Table 3.
Cardiac ultrastructure in hypertrophy, heart failure (HF), and hypertension.
| Human heart hypertrophy, hypertension, and HF | Ultrastructural changes | Quantitative TEM? | References |
|---|---|---|---|
| Dilated cardiomyopathic (DCM) hearts compared to ischemic (ICM) hearts | A large population of smaller mitochondria in dilated hearts vs. ICM hearts despite similar levels of mitochondrial dysfunction, with differential changes in mitochondrial biogenesis | Quantitative morphometric measurement of mito cellular volume density (0.3 ICM vs. 0.6 DCM μm3/μm3) | Ahuja et al., 2013 |
| Patients with DCM (250 patients) | Ultrastructural changes in cardiac myofilaments, disorganized sarcomeric structure, mitochondrial and glycogen aggregation were shown, with myofilament changes associated with ↓ survival | % myofilament changes were scored and subdivided with focal derangement, diffuse myofilament lysis, replaced by smooth endoplasmic reticulum (ER) and replaced by large filamentous masses | Saito et al., 2015 |
| Cardiac ultrastructure in human endocardial biopsies in patients with chronic HF due to different etiology | Lysosomal storage diseases, mitochondrial cardiomyopathy, autophagic degeneration, and doxorubicin (Dox)-induced cardiomyopathy, exhibit general ↓ of myofibrils, vacuolar degeneration, accumulation of glycogen granules, ↑ presence of autophagic vacuoles, and changes in mitochondrial size, shape, and number | No | Takemura et al., 2017 |
| Human DCM | The presence of autophagic vacuoles, electron-dense bodies similar to lysosomes, endosomal structures, myelinated bodies, and multivesicular bodies, with associated change of mRNA levels of 13 autophagy-related genes | No | Gil-Cayuela et al., 2019 |
| Induced pluripotent stem cells (IPSCs) from patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) | Desmosome distortion (↑ in gap and total width), and ↑ lipid droplet (LD) accumulation in response to proadipogenic stimulus | Desmosomal gap width 24 ->34 nm, total desmosome width 100 - >160 nm by ARVC, more gap width the more % LD containing cardiomyocytes | Caspi et al., 2013 |
| Phenylephrine (PE)-treated rat adult cardiac myocytes, rat LV after ascending aortic banding (HF), human HF patient LV subepicardial biopsy | Time-dependent changes (stages) occurred with mitochondrial cristae disruption, swelling, and membrane rupture in the presence of autophagosomes, significant chromatin condensation and appearance of apoptotic bodies—compared with hearts from a rat HF model, and a human patient samples HF with reduced ejection fraction (HFrEF) | % for stages A, B, B–>C, C, and D, per TEM 12k× magnified field scored for ACM control vs. PE, for rat normal vs. HF, and human normal vs. HFrEF | Chaanine, 2019 |
| Animal models of non-ischemic and non-metabolic heart disease | Ultrastructural changes | Quantitative TEM? | References |
| Guinea pig HF (8 weeks after ascending aortic constriction) | Mitochondria were fragmented and aggregated with ↓ size and area, in comparison to sham | Av. mito length ~1 −>0.75 μm, Av. mito area ~0.7 −>0.4 μm2 |
Goh et al., 2016 |
| Cardiomyocyte expression of myotrophin in mice led to heart hypertrophy at 4 weeks of age and HF at 36 weeks. of age | At 16–24 weeks of age, mitochondria became swollen, with ↓ matrix granules, at >34 weeks, with disrupted cristae. Nuclear membrane became distorted at 16–24 weeks, some rupture at >36 weeks. Myofibrillar and sarcomeric organization were disrupted at the z-line at 16–24 weeks, and worsen with appearance of myelin bodies at >36 weeks. | Scoring of changes (1–4) of mitochondria, myofibril and z-line, and cytoplasm/nucleus (0 to >45% changes initiation - progression - transition) | Gupta et al., 2010 |
| Rats with HF induced by volume overload | Nuclear chromatin condensation, myofibril damage, mitochondrial swelling and cristae damage, and the presence of electron-dense bodies in the mitochondria associated with the initiation of apoptosis | ↑ from ~10 −>~75% cardiomyocytes with apoptotic and mitochondrial changes | Treskatsch et al., 2015 |
| Adiponectin-KO mice in response to sham or mTAB | Sham hearts contain electron-dense lysosomes
Electron-dense lysosomal structures are near the mitochondria that had substantial cristae damage, in some cases membrane rupture after transverse aortic constriction (TAC) surgery |
No | Jahng et al., 2015 |
| Mouse TAC Cardiomyocyte-specific dynamin-related protein 1 (Drp1) heterozygous (+/–) knockout (KO) exacerbated and Tat-Beclin (TB1) attenuated phenotypes |
↑ Number of autophagosomes containing mitochondria per total number of mitochondria (mitophagy) 3–7 days after TAC, ↑ Mitochondrial mass as deduced from the TEM images (to ~1.3) at 24 h, ↓ at 3–5 days (0.7–0.8), and ↑ again at 30 days (1.3). Drp +/– ↑ mitochondrial mass to ~1.3 both sham and TAC 7 days, TB1 ↑ mitophagy/mitochondrial number from 0 to> ~0.16 |
Mitophagy 0 −>0.2% (days 3, 5, and 7), Mitochondrial mass changes 1 −>1.3 (24 h) −>0.7 (3–5 days) −>1.3 (30 days) by TAC, and by Drp+/– (~1.3 at sham and 7 days), TB1 ↑ mitophagy (0 −> ~0.16) |
Shirakabe et al., 2016 |
| Rat hearts containing truncated Titin | Accumulation of autophagic vacuoles in the titin truncated vs. wild-type (WT) mice, mitochondrial dysfunction, ↑ p62, LC3II, and ↓ cathepsin B | Number of autophagic vacuoles/field from 1.5 -> 4.5 | Zhou et al., 2019 |
| Dox-induced cardiomyopathy in rat | Similar mitochondrial ultrastructural changes to HF as mitochondria were swollen and with disrupted cristae | No | Babaei et al., 2020 |
| Cardiomyocyte deletion of STIM1 (KO) compare to WT (c) | DCM at 36 weeks of age. At 12 weeks of age, ↑ LD, ↓ mitochondrial length, ↑ mitochondrial density |
Av. number of LD/4400× grid2 2 (c), 3.3 (KO) Av. mito length 1150 nm (c) to 900 nm (KO) Av. number of mito/4400× grid2 18 (c) to 22 (KO) |
Collins et al., 2019 |
| Rat hearts in response to angiotensin II (Ang II) and effects of simvastatin (SIM) | Mitochondrial (mito) appearance was graded on a scale of 1–5 in response to angiotensin. SIM reversed the mitochondrial changes but ↑ numbers (No.) of LDs, autophagosomes, mitophagosomes, and lysosomes | Graded appearance; quantified: mito length, No. of swollen mito (2–8/field), mito with vacuolization, LD, autophagosome, mitophagosome, and lysosome per field | Hsieh et al., 2019 |
| Cathepsin S KO mice and/or Ang II administration | ↑ Autophagosome in the macrophages in the heart by Ang II, ↑ Autophagosome in Cathepsin S KO heart ↑↑ Autophagosome by Ang II in Cathepsin S KO, associated with more inflammatory cytokines and fibrosis |
No | Pan et al., 2012 |
Highlighted in bold are the subcellular structures observed by transmission electron microscopy (TEM).