Table 2.
Principal known effects of MBG on several organs and systems in clinical conditions.
| Organs and Systems | Pathological Processes | Effects of MBG | Clinical Studies | |
|---|---|---|---|---|
| Population | Results | |||
| Kidney and CV system | Volume-expanding conditions: essential hypertension, heart failure, PE CKD complications: LVH, UC, myocardial fibrosis, diastolic dysfunction |
Sodium and fluid retention, organ fibrosis and remodeling, vascular and microcirculation alterations, activation of oxidative stress pathways | Keppel, M.H., [19] et al.; in patients with arterial hypertension; plasma MBG levels were measured in 40 patients, of whom 11 patients had primary aldosteronism (PA) and 29 patients had essential hypertension after exclusion of PA. | MBG concentrations increased, but not significantly, and showed a direct correlation trend with albuminuria and proteinuria. |
| Bolignano, D., [20] et al.; cohort of 29 patients on HD vs. healthy controls. | MBG levels in HD patients were significantly higher than in healthy controls and significantly reduced in HD patients experiencing IDH during follow-up. Inverse correlations were found between the absolute number of IDH episodes per person and, respectively pre-dialysis MBG, 2 h MBG and HD-end MBG. MBG levels remained basically unchanged in HD patients with no documented IDH episodes during follow-up. | |||
| Piecha, G., et al. [21]; 68 HD patients vs. 68 age-, gender- and blood pressure-matched subjects without CKD. | Mean plasma MBG immunoreactivity was significantly higher in HD patients compared with subjects with normal kidney function. In HD patients, plasma MBG was higher in men than in women, while this difference was not observed in subjects with normal kidney function. | |||
| Bolignano, D., et al. [22]; 46 HD patients vs. healthy controls. | MBG levels were significantly higher in HD patients than in healthy controls. A statistically significant trend in MBG levels was found across different patterns of LV geometry, with the highest values in eccentric LVH. MBG levels were higher in presence of diastolic dysfunction. | |||
| Jablonski, K.L., et al. [23]; middle-aged/older adults with moderately elevated systolic BP, but otherwise free of CV disease, diabetes, kidney disease and other clinical disorders. | Urinary MBG excretion decreased after 5 weeks of low sodium diet compared with 5 weeks of high sodium, while plasma MBG levels were not different between sodium conditions. Urinary MBG excretion was related to urinary sodium excretion and blood pressure measurements | |||
| Strauss, M., et al. [24]; young, apparently healthy Black and White adults (60). | A persistent positive association between carotid-femoral pulse wave velocity and MBG excretion was found in women but not in men. High endogenous MBG levels may contribute to large artery stiffness in women through pressure-independent mechanisms | |||
| Strauss, M., et al. [25]; young, apparently healthy Black and White adults (63) | LV mass, end diastolic volume and stroke volume were positively related to MBG excretion. The relationship between LV mass and MBG excretion was evident in women but not in men. Women may be more sensitive to MBG effects on early structural cardiac changes | |||
| Feto-placental unit | Sex and gender medicine: pregnancy diseases, PE | Endothelial dysfunction, apoptosis, release of angiogenic factors, umbilical arteries fibrosis | Lopatin, D.A., et al. [26]; 6 non-pregnant women, 6 normotensive age-matched pregnant controls and 11 patients with PE. | MBG levels significantly increased in PE pregnant women. MBG induced a contractile response of isolated rings of human mesenteric arteries in a concentration-dependent manner. MBG has a pathogenic role in PE. |
| Agunanne, E., et al. [14]; 17 pre-eclamptic women and 46 normotensive pregnant women in various gestational periods. | Serum and urinary levels of MBG were significantly greater in pre-eclamptic women than normotensive pregnant women. MBG can be used for prediction and diagnosis of PE. | |||
| Nikitina, E.R., et al. [27]; 16 pre-eclamptic pregnant women and 14 gestational age-matched normal pregnant women. | Serum and urinary levels of MBG increased in pre-eclamptic women compared with normal pregnant women. MBG, through a Fli-1-dependent mechanism stimulates collagen synthesis in umbilical arteries, leading to the impairment of vasorelaxation. MBG may represent a potential target for PE therapy. | |||
Legend: CKD: chronic kidney disease; CTB: cytotrophoblast; ESKD: end-stage kidney disease; Fli-1: friend leukemia integration 1 transcription factor; HD: hemodialysis; IDH: intradialytic hypotension; LV: left ventricle; LVH: left ventricular hypertrophy; MBG: marinobufagenin; PE: pre-eclampsia; UC: uremic cardiomyopathy. Specification: numbers in parentheses indicate the reference number in the text.