A Role of Thyroid Hormones in Acute Myocardial Infarction: An Update

Abstract

The acute coronary syndrome is one of the commonest life-threatening illnesses. It encompasses the clinical spectrum of acute myocardial ischemia and includes unstable angina and acute myocardial infarction both with and without ST segment elevation. The acute coronary syndrome can be attributed to a significant hemodynamic insult that leads to atherosclerosis of the epicardial coronary arteries. The main causative risk factors, such as obesity, smoking, and alcohol intake, increase the burden of acute coronary syndrome. Owing to an increase in the utilization of antioxidants, the antioxidant capacity decreases concerning the scavenging of lipid peroxides. Moreover, the thyroid hormones are important regulators of the expression of cardiac genes, and many of the cardiac manifestations of thyroid dysfunction are associated with alterations in triiodothyronine-mediated gene expression. Cardiovascular signs and symptoms of thyroid disease are among the most acute clinically relevant findings that occur in combination with both hypothyroidism and hyperthyroidism. By understanding the cellular mechanism of the action of thyroid hormones on the heart and cardiovascular system, it is possible to explain rhythm disturbances and alterations in cardiac output, blood pressure, cardiac contractility, and vascular resistance that result from thyroid dysfunction. Oxidative stress is thereby induced, together with a decrease in antioxidant capacity for overcoming oxidative stress, which leads to endothelial dysfunction, subsequent atherosclerosis, and, ultimately, acute myocardial infarction. The implications for the identification of the effects of thyroid disease on acute myocardial infarction include the observation that restoration of normal thyroid function repeatedly reverses abnormalities in cardiovascular hemodynamics.

1. INTRODUCTION

Chronic heart disease, manifested by myocardial infarction (MI), is one of the leading causes of sudden death and is therefore considered a life-threatening disease. Most patients over the age of 45 are more likely to develop myocardial infarction, but young women and men may also develop MI. Prompt medical attention is mandatory for patients with acute myocardial infarction of all ages, but patients in older age groups have a higher risk of mortality and morbidity than patients in younger age groups. In the United States, 85 percent of the population dies from acute MI, and the highest rate is 65 years and over. The occurrence of Acute Coronary Syndrome (ACS) at a young age has prominent psychological effects, financial restrictions, and morbidity. Physical inactivity, obesity, and smoking are the factors that increase the prevalence of AMI and coronary heart disease in patients of young age and can only be cured with the appropriate diagnosis and treatment [1]. According to the WHO report, 14 million people die every year from MI [2]. In myocardial infarction, one or more coronary arteries that supply oxygenated blood to heart muscles are bunged, causing cardiac muscle infarction [3]. The transmularity and reversibility of myocardial injury depend on the extent of coronary artery blockage. Many other factors intensify the damage, such as IPC (Ischemic preconditioning) or collateral circulation to the affected area of the myocardium. The wavefront phenomenon states that cell death occurs in the subendocardium in six hours that progressively and slowly moves toward the subepicardium [4]. Fat and cholesterol form plaque accumulation in the coronary arteries, ensuring blockage and causing coronary artery disease (CAD). The first clinical symptom of this plague formation is angina pectoris [5]. The longer persistence of this obstruction can result in heart muscle necrosis, thereby causing a myocardial infarction. In medical emergencies, if MI is not properly treated, it can permanently damage the heart muscle. [6,7].

Four groups have been developed on the cause of MI: Atheroscytus CHD, Non-Atheroscytus CHD, Hypercoagulable State, and the relationship between misused substances and MI. Among all groups, there is a significant overlap, but it would help the practitioner toward unified management. There is an increasing burden of this disease in the future due to its rising prevalence and risk factors in children and young people and adults. The most common risk factor associated with heart disease is smoking, with a prevalence of 9% in young people and adolescents. Obesity has increased threefold in children and young adults in the UK in the last 20 years and now has been a growing concern [8]. For coronary heart disease, insulin resistance is a marker, and in the USA, 24% of school-going children have insulin resistance [1]. Two-thirds of the populations of young people diagnosed with MI have been found to have insulin resistance and metabolic syndrome [9]. There has been a noticeable increase in the prevalence of cardiac diseases among definite ethnic groups, that is, Indian Asians. These people get MI at a very young age [10]. In the young population, having nontraumatic chest pain of a nontraumatic nature could result in myocardial infarction, and the most typical cause is the excessive use of cocaine [11]. Therefore, it became clear that in the coming years, patients younger than 45 years would have a high prevalence of coronary heart disease.

Cardiovascular disease (CVD) is the main cause of death in Western countries. According to the WHO, 17.9 million people die annually due to MI, which accounts for 32 percent of the world’s mortality. Of the 17 million premature deaths in 2019 from NCDs, 38% were caused by cardiovascular disease. More than 3/4 of all cardiovascular deaths worldwide have been reported in middle- and low-income countries [12]. Risk factors for coronary artery disease (CAD) include high BP, elevated cholesterol levels, smoking, abdominal obesity, high-risk diet, moderate alcohol consumption, physical inactivity, psychological stress, and diabetes mellitus [13]. Symptoms that are reported at the time of myocardial infarction commonly include crushing pain in the chest, feeling of discomfort or heaviness, nausea, palpitation, vomiting, feeling faint, weak or dizzy, indigestion like feeling, symptoms of flu, shortness of breath, pain in shoulder/jaw/back/head, panic feelings, and collapse [14].

The cardiovascular system is known to be affected in several ways by hypothyroidism or hyperthyroidism. However, the effects of thyroid dysfunction on the cardiovascular system are easily detectable, especially in the case of hyperthyroidism. The evidence of long-term thyroid dysfunction on cardiovascular outcomes is less clear [15]. However, the Rotterdam study concluded that patients with subclinical hypothyroidism have a notable increase in the prevalence of aortic atherosclerosis and MI [16]. Receptors for thyroid hormone are present in vascular endothelial and myocardial tissues and are sensitized to changes in the concentration of thyroid hormone in the circulation. The cardiovascular system is adversely influenced even if there is a subtle change in thyroid hormone, i.e., hypothyroidism or hyperthyroidism. There are several mechanisms linking two conditions: dyslipidemia, blood pressure changes, endothelial dysfunction, and the direct effects of thyroid hormones on myocardial function. Various interventional trials have shown that the treatment of subclinical thyroid diseases improves cardiovascular risk factors. During the last 20 years, evidence has supported the association between AMI and abnormal thyroid function following unfavorable cardiovascular outcomes. Experimental studies have shown that after AMI, thyroid hormone plays an important role in reducing the size of the infarct and improving myocardial function [17]. Vascular and cardiac effects are shown by thyroid hormones, and in most tissues, biochemical reactions are also regulated by thyroid hormones. Some patients with AMI have been reported to have low levels of biologically active T3 (triiodothyronine), which shows that thyroid hormone metabolism is altered [18]. These patients with low T3 had AMI with congestive heart failure after heart surgery and in patients with variant serious systemic diseases [18, 19]. In serious chronic heart failure, acute myocardial infarction, and heart surgery, low T3 levels are common [20-22]. The high mortality rate is associated with low TH levels in plasma in both patients with AMI and heart failure [18]. Because the cardiovascular system is an important target of thyroid hormone action, this review highlights various aspects of thyroid abnormalities concerning cardiovascular disease, particularly acute myocardial infarction.

2. RED CARPET FOR THYROID HORMONE

The thyroid gland consists of two lobes, so it is easily accessible in places in the human body for both inspection and inspection. The thyroid gland is coupled with an isthmus. The thyroid tissue is light brown with a shiny cut surface. A delicate fibrous capsule weighing 15-25 grams surrounds the gland [23]. The primary synthetic steps involved in the regulation of TSH include endocytosis secretion, organification, iodide transport, coupling, and synthesis of thyroglobulin (Tg). After TSH stimulation, iodide is removed from the capillary network of thyroid cells and moves to the apex of the cell. T4 and some T3 are produced when tyrosine molecules are attached to them. In organification, iodine binds to tyrosine residues, a component of the 660-kDa glycoprotein Tg molecule. Within the follicles of the gland in the colloid, T3 and T4 are stored. They are released together or before release, and some T4 is deiodinated to T3 via a two-step process that is also influenced by TSH or proteins that bind to TSH receptors [24]. Multinodular goiters and toxic adenomas are continuously activated by the mutation of the TSH receptor. Goiter has also been known to be caused by some defects in the synthesis of Tg, although these are rare cases. For the treatment of thyroid cancer, serum Tg serum values are highly effective [25].

3. HYPOTHYROIDISM AND ITS EFFECT ON CARDIOVASCULAR PHYSIOLOGY

Thyroid hormone deficiency is a form of hypothyroidism caused by inadequate thyroid hormone secretion or by insufficient TSH secretion or thyrotropin-releasing hormone secretion, causing reduced thyroid hormone secretion. Symptoms may vary from patient to patient. In some patients, it may be asymptomatic; however, in rare cases, it leads to coma, i.e., myxoedema coma. The disease is more common, particularly in women over 40 years of age. Hypothyroidism is widespread in elderly weak patients of both sexes [26]. Globally, iodine deficiency is the leading cause of hypothyroidism. Hashimoto’s thyroiditis disease appears to be the most common due to inadequate iodine intake [27].

The symptoms of heart failure are consistent with the cardiovascular influence of hypothyroidism. Cardiovascular output often decreases to half due to myxedematous changes that occur in the heart that eventually result in lowered contractility, pulse rate, and stroke volume. The pericardial effusion is perceptible. Many of these pathological changes can be reversed via the replacement of thyroid hormone; however, caution is needed only in elderly patients to avoid intensification or precipitating angina pectoris, AMI, congestive heart failure of a congestive nature, and ventricular arrhythmias [28, 29]. According to estimates, approximately 4.6 to 8.6 million Americans meet the clinical diagnosis guidelines for hypothyroidism, which is subclinical and does not have any significant symptoms [30]. Despite the lack of symptoms, SCH treatment indicates that it is based on physiological effects that eventually elevate TSH. The relationship between cardiovascular health and TSH elevations has been very well studied; nevertheless, subjects with SCH are still debatable [31, 32]. Hak et al. [33] reported that there is an independent association of SCH with an increase in aortic atherosclerosis and MI rate in old-age women. Walsh et al. [34] showed that the independent predictor of coronary heart disease is SCH, and patients with SCH had significantly more fatal/nonfatal CHD events. Rodondi et al. [35] reported that older patients with SCH had no increased CHD events, PAD, stroke, cardiovascular mortality, or all-cause mortality rate compared to euthyroid controls. In subjects with SCH, the researchers found higher absolute levels of cholesterol and increased recurrence and incidence of CHF. Studies indicate that with SCH, cardiovascular risk increases. Recently, a study evaluating T3 doses in patients with STEMI and reduced or borderline circulating T3 hormone showed that thyroid hormone plays a significant role in the repair and protection of myocardium throughout unfavorable stress situations, as well as in ischemia and acute MI [36].

4. HYPERTHYROIDISM AND MYOCARDIAL INFARCTION

The excess production and release of thyroid hormone into the circulation is termed hyperthyroidism. Extravagant thyroid hormone causes some nonspecific changes, including nervousness, weight loss, fatigue, palpitations, or rapid heartbeat corresponding to arterial fibrillation, heart intolerance, and high-output congestive heart failure (CHF). Thickening of the left ventricle is caused by excess thyroid hormone and is associated with increased CHF risk. An association has been found between dilated cardiomyopathy with thyrotoxicosis, failure of the right heart with pulmonary hypertension, and diastolic dysfunction. The presentations of thyrotoxicosis among younger patients are anxiety, tremor, and hyperactivity. In contrast, older patients have further cardiovascular symptoms that include atrial fibrillation and dyspnea with loss of weight. The degree of biochemical abnormality does not always correlate with the clinical presentation of thyrotoxicosis. Excess thyroid hormone could cause palpitations, tachycardia, exercise disturbance to some degree, and a wide pulse rate [37].

In hyperthyroidism, cardiac output is 50-300% higher than that in normal subjects. This increase is due to the combined effects of a decrease in systemic vascular resistance, an increase in heart rate, a rise in the left ventricular ejection fraction and contractility, and an increase in blood volume increases [38]. According to a study administering arterial vasoconstrictors, i.e., phenylephrine and atropine, reduced blood flow to the peripheral region and reduced cardiac output by almost 34% in patients who had hyperthyroidism, but when tested in normal subjects, it showed no effects [39]. Hyperthyroid patients could have increased left ventricular diastolic and systolic contractile function and modified expression of calcium regulatory and contractile proteins, as reported by Ojamaa et al. [40]. The administration of β adrenergic receptor antagonists in patients with hyperthyroidism may slow down the heart rate; however, it does not change the diastolic or systolic contractile performance [41]. Therefore, it confirms that there is a direct action of the thyroid on the cardiac muscles.

5. THE ROLE OF THYROID HORMONE IN CARDIAC REMODELLING

The importance of thyroid hormone in organ remodeling regarding tissue and organ resurrection, such as metamorphosis of amphibians or zebrafish, has been revealed [34,42]. Attractively, the metamorphosis of amphibians that enables life to arise from the aquatic environment on Earth is utterly dependent on thyroid hormones. This gene programming is conserved in the evolutionary life of mammals, with TH being condemnatory for the development of the embryonic heart and the influence of many aspects of regeneration by the reactivation of developmental gene programming afterward in adult life [37]). AKT signaling is one of the main players in the cell feedback of the heart to stress. Moreover, it regulates physiological growth. Thus, pathological hypertrophy is aggravated by chronic blockade of AKT [43]. The administration of TH in myocardial infarcted mice had a favorable impact depending on the degree of thyroid-induced AKT phosphorylation [44].

6. THYROID HORMONE AND THE RESPONSE OF THE MYOCARDIUM TO STRESS

Many changes in TH–TR homeostasis can be induced by myocardial ischemia, resembling those occurring during heart development at the embryonic level. The characteristic feature is TRα1 re-expression along with intensified growth kinase signaling during cardiac hypertrophy and a decrease during heart failure [44]. This interrelation shows a possible link between TRα1 and growth signaling. Therefore, in the phenylephrine-induced cell growth model, the pathways from the cytosol to the nucleus, PEP resulted in the reorganization of the TRα1 receptors. Regarding the cellular stress response, physiological modifications have been observed. Thyroid hormone removal from the culture medium, TRα1, showed a suppressive action that can result in cell dedifferentiation along with the formation and structures of undefined cell forms and structures such as filopodia, which contained disoriented, profuse myofibrils and increased β-MHC.

In contrast, the incorporation of thyroid hormones in a culture medium results in cell differentiation through TRα1 transport of TR1 to its ligand [45]. This series of experiments revealed that TH signaling is imperative for the cardiac cell response to stress and has been shown to save cardiac cells from stress-induced dedifferentiation. In light of observations made in the cell-based model, many animal studies on MI have shown that TH could have a reparative effect on damaged myocardium [46]. Consequently, apoptosis and infarct size in animals were reduced by treating thyroid analogs or TH initially after coronary ligation [46, 47]. Remarkably, TH favorably remodeled the nonischemic and viable myocardium. The development of hypertrophy of the heart is accelerated by TH and is distinguished by the adult pattern of the expression of MHC isoforms. Inadvertent normalization of wall stress is caused by this response and is a crucial factor in oxygen consumption and myocardial performance [48].

Treatment with thyroid hormones can critically determine the mechanical effectiveness of the myocardium and has a prominent effect on cardiac structure [49, 50]. TH chiefly reshapes the heart to an ellipsoid shape from a spherical shape after MI, either late or early. The effect of thyroid hormone on cardiomyocyte remodeling was observed at the molecular level. Therefore, factors involved in the transcription of mitochondrial DNA and biogenesis transcription and cardioprotective molecules, i.e., HSP70 and calcium transport proteins, are overexpressed in thyroid treatment. Moreover, TH modulates the regulation of PKCε and PKCα [44-46].

7. THYROID HORMONE AND CARDIO-PRESERVATION

However, thyroid hormones increase oxygen consumption and decrease heart glycogen but are believed to protect the heart in ischemic situations. Preconditioning of the ischemic heart and pretreatment with TH had homogeneous functional feedback to the ischemic insult, distinguished by a prominent increase in postischemic functional recovery and the exacerbation of diastolic dysfunction in the ischemic period, that is, ischemic contracture. This effect was mediated by the suppression of the proapoptotic MAPK p38 signaling pathway. This paradox is explained by the fact that physiological growth shares distinctive pathways involved in the stress response. Hence, activation of redox-regulated signaling pathways that determine cell differentiation triggers cardioprotective molecules such as heat shock proteins, which can increase cell tolerance against ischemia. Rat model studies revealed that TH is acutely capable of protecting the myocardium through its nongenomic action. Therefore, T3 has no impact on the uninjured myocardium, which significantly improves postischemic recovery and restricts apoptosis in the impaired myocardium, which is reconciled by suppressing pro-apoptotic MAPK p38. Interestingly, the nongenomic effect of T3 was initiated by the TRα1 receptor, which probably describes the failure of T4 to border reperfusion injury [45, 46].

8. MECHANISM OF MYOCARDIAL INFARCTION IN RELATION WITH THYROID HORMONE CHANGES, OXIDATIVE STRESS, AND LIPID PEROXIDATION

In TSH feedback, the thyroid gland synthesizes T3 & T4. T4 is secreted primarily by the thyroid gland and is converted to T3 by 5-monodeiodination in skeletal muscle, kidney, and liver [51]. The heart depends on serum T3, as there has been no notable activity of intracellular myocyte deiodinase, and T4 & T4 are transported inside the myocytes [52]. The cellular action of T3 is exerted through binding to the nuclear receptors of thyroid hormone (TR). Such receptor proteins mediate transcriptional induction when they attach to TREs (thyroid-hormone response elements) [1]. TRs belong to the superfamily of steroid receptors. TREs are bound to TRs in the presence and absence of ligands. TRs bind as a homodimer or more often as a heterodimer to TREs with one of the three isoforms of retinoid X receptor (RXRβ, RXRγ, or RXRα) [53]. TR binding to T3 induces transcription, while in the absence of T3 binding, transcription is repressed [54].

The effects of thyroid hormone on the peripheral vasculature and heart comprise reduced systemic vascular resistance (SVR) and increased contractility of the left ventricular heart rate and blood volume. Thyroid hormone produces slightly stronger resistance in the peripheral arterioles through an absolute effect on the vascular smooth muscles and reduced arterial pressure when found in the kidneys, eventually activating the RAA (renin-angiotensin-aldosterone) system and increasing renal sodium (Na) absorption. T3 also increases erythropoietin synthesis, which eventually leads to increased red cell mass. The increase in preload and blood volume is stimulated by these changes. In hyperthyroidism, these compounds affect the cardiac output 50 to 300% higher than that of normal healthy persons, while hypothyroidism shows opposite cardiovascular effects, and cardiac output may fall by 30 to 50% [55]. It is crucial to recognize that normal cardiovascular hemodynamic repair can be overcome with a prominent increase in heart rate at cessation in hypothyroidism treatment. In vascular smooth muscle cells, thyroid hormone mediates outcomes via impacts of both nongenomic and genomic actions. Endothelial nitric oxide synthase and membrane ion channels are targeted by nongenomic actions, which decreases the SVR [56]. The reduction in VSM leads to a reduction in arterial pressure and resistance, which increases cardiac output. Elevated endothelial NO may be produced as a result of the effects of TR that are mediated by T3 on the AKT pathway of protein kinase wither through genomic or nongenomic mechanisms [57,58]. NO synthesized in endothelial cells operates in a paracrine manner on adjoining VSM cells to ease vascular dilatation. In hypothyroidism, there is reduced arterial compliance, which promotes elevated SVR. Obstructed vasodilatation that is endothelium dependent due to NO depletion of NO has been explained in subclinical hypothyroidism [59]. In hyperthyroidism, decreased SVR increases blood volume and perfusion in tissues of the periphery. The association of increased vascularity with hyperthyroidism suggests that T3 increases the capillary density via expanded angiogenesis [43].

Thyroid hormone is an important regulator of cardiac gene expression, and most cardiac dysfunction of the thyroid is associated with changes in gene expression that are mediated by T3 [60]. Serum cholesterol levels in patients with hyperthyroidism have been reported to be elevated. Openly, hyperthyroidism is distinguished by higher cholesterol, LDL, and apo-lipoprotein B. Whereas the prevalence of overt hypothyroidism in hypercholesterolemic patients is approximately 1.3 to 2.8%, 90% of patients diagnosed with hypothyroidism have higher cholesterol levels [61]. Changes in the lipid profile are also evident in subclinical hypothyroidism. In essence, few studies have shown increased LDL levels in subclinical hypothyroidism and can be reversed only with the replacement of thyroid hormone, while other studies showed that the increase in total cholesterol level in subclinical hypothyroidism does not have significant changes in the LDL profile [62, 63]. The mechanism reported in hyperthyroidism for the development of hypercholesterolemia comprises a decrease in fractional LDL clearance due to decreased LDL receptors in the liver [61, 64]. The destructive metabolism of cholesterol to bile is mediated by an enzyme, cholesterol-7α-hydroxylase [65]. This is a liver-specific enzyme that is negatively regulated by T3 and may also contribute to reduced catabolism and elevated serum cholesterol levels linked to hypothyroidism. High serum lipid levels in subclinical hypothyroidism and underlying disease are linked to the risk of heart disease [34, 65]. If left untreated, the dysfunction in the lipid profile along with diastolic hypertension is related to hypothyroidism and may be further influenced by the thickening of the arterial walls. Hyperthyroid patients have typical indications and symptoms, numerous related to the heart and the cardiovascular system [66]. Hyperthyroidism and thyrotoxicosis are linked with tachycardia, palpitation, dyspnea during exertion, exercise intolerance, wide pulse pressure, and arterial fibrillation. Cardiac contractility is intensified, and heart rate and cardiac output are increased. In normal subjects, cardiac output could increase by 50 to 300%, and as a result, the combined effect of elevations in heart rate at rest, ejection fraction, contractility, and volume of the blood with a decrease in SVR [38].

In a few rare cases, patients with hyperthyroidism can develop chest pain and changes in ECG that are eventually indicative of cardiac ischemia. Old age patients who have a suspected coronary artery disease show increased oxygen demand in the heart in response to the increase in cardiac contractility and capacity linked to thyrotoxicosis. However, intermittently younger patients with unknown cardiac disease can have similar findings [67]. In those patients, coronary angiography indicates the normal anatomy of the coronary artery, and the reasons for these findings have been associated with coronary vasospasm. Successful therapy of hyperthyroidism has been associated with the reversal of these typical symptoms [68].

The most uncommon cardiovascular signs and symptoms related to hyperthyroidism may include mild hypertension (diastolic), bradycardia, narrowed pulse pressure, fatigue, and cold intolerance [69]. The effect of symptomatic hyperthyroidism is 3% of the population of adult women and is linked to a higher SVR, compromised cardiac contractility and cardiac output, advanced atherosclerosis, and CAD [68], which could be the consequence of diastolic hypertension and hypercholesterolemia. Hypothyroid patients have other cardiovascular atherosclerotic disease risk factors and a prominent risk of stroke risk. Changes in BP, fluctuations in lipid metabolism, decreased cardiac contractility, and increased SVR indicate escort hypothyroidism and can potentially be reversed through the replacement of thyroid hormone [70]. Metabolic inflammatory biomarkers include RAGE and interleukin-1. In Fig. (1), Adhesive molecules, i.e., chemokines, TNF-a, and IL-1 levels, help assess cardiovascular risks [71, 72]. IL1R1 with ILIβ ligands is increased in CVD, obesity, activated megakaryocytic activity, infection, and atherothrombosis [73]. Secreted chemokines act as hypertensive biomarkers, and oxidative and inflammatory markers are the primary markers for diagnosing the disease [74]. A pleiotropic cytokine, IL-1α, that modulates many life processes. To date, studies have illustrated that IL-1, along with its IL-1Rα regulator, is involved in various cardiovascular diseases, such as MI, atherosclerosis, myocarditis, and cardiomyocytes, through TL-1 gene mutation, which increases inflammatory mediator expression. In MI, TNF-α is involved in inflammation by triggering apoptosis of cardiac cells. Various studies, both in vitro and in vivo, have investigated whether the heart cells in the presence of mechanical stress produce an elevated amount of TNF-α. During overabundant pressure, TNF-α contributes to unfavorable LV modeling, resulting in impairment of the ventricular wall. In atherosclerosis, the chemokines of the vascular wall are increased by TNF-α, the expression of ICAM-1 and VCAM-1, and increased proliferation and migration [75]. TNF-α released from inflammatory cells increases artery infiltration and activates other cytokines, increasing plaque instability that leads to thrombus formation [76]. Elevated ROS production is involved in oxidative stress that overreaches the endogenous antioxidant defense mechanism, which is directed at the modification of the oxidation of DNA, carbohydrates, proteins, lipids, and macromolecules. Some of these altered molecules have absolute effects on the function by inhibiting the function of the enzyme, but few only exhibit oxidative stress. Cellular proteins that are functional in nature, their oxidative modifications, are a basal step in cellular injury. Therefore, the identification of markers of oxidative stress can consolidate more than one process that activates the pathogenicity of the cardiovascular system. Summation of lipoproteins within the blood vessels intima and they begin to oxidize by the activity of radicals that are oxygen-free and are produced either by endothelial cells or macrophages. Low-density oxidized lipoproteins are engulfed through macrophages by the process of endocytosis with scavenger receptors, which are defined from LDL receptors. LDLs are magnified in other phagocytes and macrophages and form cells known as foam cells.

Fig. (1).

Biochemical changes associated with thyroid hormones with acute myocardial infarction. Abbreviation: TNF-α (tumor necrosis factor alpha), IL (interleukin), CAT (catalase), SOD (superoxide dismutase), PUFA (polyunsaturated fatty acids), LDL (low-density lipoproteins), NO (nitric oxide), AOPPs (advanced oxidation protein products), TR (thyroid receptor), DIO (deiodinase), CAD (coronary artery disease), AMI (acute myocardial infarction), OH (hydroxyl).

Fatty streaks of atheroma plaques are formed by foam cells in the tunica intima of the arteries. Foam cells contain LDL cholesterol. The term “bad cholesterol” is labeled LDL cholesterol. It is an atherosclerotic marker. The way to remove bad cholesterol from the blood vessels in the foam cells. Foam cells do not exude any signs or symptoms, but they are the unit of origin of atherosclerosis. Foam cells are very small in size and can be detected by the fatty plaque under the microscope. The cholesterol named ‘good cholesterol’ is HDL which eliminates dangerous bad cholesterol from vessels or from where it does not belong [7]. Foam cells are not dangerous, but they can be a problem if they accumulate at a particular point, thus forming an atherosclerosis necrotic plaque. If the hairy cap made of fibers intercepts the necrotic plaque from overflowing inside the lumen of the vessels, a clot can be formed, which ultimately leads to emboli that occlude the smaller vessels. After small vessel blockage, it results in ischemia and corresponds to MI and stroke, the two most related causes of death associated with the cardiovascular system.

CONCLUSION

The signs and symptoms of cardiovascular disease are among the most pervasive clinical findings associated with hyperthyroidism and hypothyroidism. Based on the understanding of the cellular mechanisms of thyroid hormone action on the heart and cardiovascular system, it is possible to explain the changes in cardiac output, cardiac contractility, blood pressure, vascular resistance, and arrhythmias resulting from thyroid dysfunction. This generates an oxidative stress condition along with a reduction in antioxidant capacity to triple over this stress, leading to endothelial dysfunction leading to atherosclerosis and ultimately acute myocardial infarction. This causes oxidative stress and reduces the antioxidant ability to overcome the stress, causing endothelial dysfunction, atherosclerosis, and eventually acute myocardial infarction. The importance of understanding the effects of thyroid disease on AMI also derives from the observation that normal thyroid function restoration often reverses abnormal cardiovascular hemodynamics.

LIST OF ABBREVIATIONS

MI

Myocardial Infarction

ACS

Acute Coronary Syndrome

CAD

Coronary Artery Disease

CVD

Cardiovascular Disease

AUTHORS’ CONTRIBUTIONS

RR and THJ conceived the review. RR, AU, GQC and BM collected the information and wrote the paper. RR, THJ, AU modified the manuscript and AU Formal analysis. All authors contributed to the article and approved the submitted version.

CONSENT FOR PUBLICATION

Not applicable.

FUNDING

The authors declare that there are no sources of funding to be acknowledged.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.