OBJECTIVETo investigate the association between clinical and histopathological features in patients with left ventricular non-compaction cardiomyopathy (LVNC).

METHODSHistopathological examinations were made on 11 LVNC recipient hearts from June 2004 to June 2014 in Fuwai Hospital, myocardial ultrastructure changes were detected using transmission electron microscopy. Association between clinical and pathological features were analyzed.

RESULTSPatients were (24 ± 11) years old. There were 6 patients with mucus matrix LVNC, 3 patients with fibrous fatty infiltration, and 2 patients with cardiomyocytes proliferation. The gross morphological changes of LVNC hearts were characterized by numerous and prominent trabeculations with deep intratrabecular recesses in left ventricular myocardium. Ratios of the thicker noncompacted endocardial layer (N) and thin epicardial compacted layer (C) (N/C ratio) were ≥ 2.0, and the most serious lesions were located in the left ventricular apex, and followed by the left ventricular free wall. Histological microscopic examinations evidenced numerous matrix-like material and immature cardiomyocytes on endocardial tissue. Transmission electron microscopy revealed mitochondrial abnormalities on morphology, number, and distribution, underdeveloped cardiomyocytes and anomalies of intercalated disc structure, increased deposition of extracellular matrix-like substance and perinuclear glycogen. Pathological changes on cytoplasmic matrix and intercalated disc were present in all three tissue types of LVNC in this cohort and mitochondria hyperplasia was detected in patients with fibrous fatty infiltration. Heart weight ≥ 350 g is often associated with increased number of mitochondria. Increased cytoplasmic matrix was often detected in patients with LVEF ≥ 30% while intercalated disc anomalies were often detected in patients with LVEF < 30%.

CONCLUSIONHistological changes were closely related clinical features in patients with LVNC.

Adolescent ; Adult ; Cardiomyopathies ; pathology ; Endocardium ; pathology ; Heart Ventricles ; pathology ; Humans ; Mitochondria, Heart ; pathology ; Myocardium ; pathology ; ultrastructure ; Young Adult

Acute myocardial infarction is one of the major causes of mortality worldwide. Reperfusion in a timely fashion is the most effective way to limit infarct size. However, reperfusion can itself prompt further myocardial injury. This phenomenon is commonly known as myocardial ischemia-reperfusion (IR) injury. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme metabolizing acetaldehyde and toxic aldehydes. Increasing evidence has revealed a cardioprotective role of ALDH2 in myocardial IR injury. Evidence from animal studies has shown that ALDH2 diminishes acute myocardial infarct size, ameliorates cardiac dysfunction and prevents reperfusion arrhythmias. The activity of ALDH2 is severely compromised if it is encoded by the mutant ALDH2*2 gene, with an incidence of approximately 40% in Asian populations. Epidemiological surveys in the Asian population have depicted that ALDH2 polymorphism is closely associated with higher prevalence of acute myocardial infarction and coronary artery disease. Therefore, targeting ALDH2 may represent a promising avenue to protect against IR injury. This review recapitulates the underlying mechanisms involved in the protective effect of ALDH2 in cardiac IR injury. Translational potential of ALDH2 in the management of coronary heart disease is also discussed.
Aldehyde Dehydrogenase ; metabolism ; Animals ; Heart ; physiopathology ; Humans ; Mitochondria, Heart ; enzymology ; Myocardial Reperfusion Injury ; Myocardium ; pathology

Burns ; complications ; pathology ; physiopathology ; Humans ; Mitochondria, Heart ; pathology ; Myocardial Ischemia ; etiology ; prevention & control

OBJECTIVETo investigate the influence of hypoxia induced microtubule damage on the opening of mitochondrial permeable transition pore (MPTP)of cardiac myocytes and on the decrease of respiratory function in rat.

METHODSPrimary cultured myocardial cells from 30 neonatal rats were randomized as normoxic group (A), hypoxia group (B), normoxia with microtubule destabilizing agent group (C, with treatment of 8 micromol/L colchicines for 30 minutes before normoxia), and hypoxia with microtubule stabilizing agent group (D, with treatment of 10 micromol/L taxol for 30 minutes before hypoxia). beta-tubulin immunofluorescence ,the opening of mitochondria permeability transition pore, and the mitochondrial inner membrane potential were detected at 0.5, 1, 3, 6 and 12 post-treatment hours (PTH), and the mitochondrial respiratory function was determined by MTT method. The changes in these indices were also determined in A group at the corresponding time-points.

RESULTSObvious damage of polymerized microtubule, opening of MPTP, mitochondrial inner membrane potential loss and decrease of myocardial respiratory activity were observed in both group B and C at 0.5 PTH, and they became more and more serious afterwards. However, the changes in the above indices in D group were much better than those in B group (P < 0.05 or 0.01), and no difference was found between D (92.8 +/- 4.0)% and C [(100.0 +/- 0.0) %, P > 0.05] groups.

CONCLUSIONHypoxia played a role in the myocardial microtubule damage as well as in the opening of MPTP. Moreover, hypoxia could also impair the mitochondrial respiratory function. Microtubule destabilizing agent could reproduce well the process of hypoxia induced microtubule damage, while the stabilizing agent exerted protective effect by improving the transition of mitochondrial permeability and the mitochondria respiratory function.

Animals ; Cell Hypoxia ; Cells, Cultured ; Hypoxia ; metabolism ; pathology ; Membrane Potential, Mitochondrial ; Microtubules ; pathology ; Mitochondria, Heart ; metabolism ; pathology ; Myocytes, Cardiac ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley

AIM AND METHODSUsing in vivo myocardial injury model induced by Isoproterenol (ISO) and the model induced by in vitro global heart ischemia/reperfusion (I/R) in rats, we observed the effects of myocardial ischemia and ischemia/reperfusion on bio-membranes of mitochondria and sarcolemma injury.

RESULTSISO (5 mg/kg, s.c.) and I/R (20 min/20 min) damaged myocardial bio-membranes of rat, in which the lipid peroxidation of mitochondria was significantly increased, the activity of phospholipase A2 was activated and the contents of phospholipid and free fat acid were decreased and increased significantly, respectively. The membrane lipid fluidity and the activities of Ca(2+) -ATPase of mitochondria and Na+, K(+) -ATPase of sarcolemma were significantly lowered. In addition, the respiration function of mitochondria was declined and the oxidative phosphorylation of respiratory chain was uncoupled, which resulted in the decrease in the production of high energy phosphoric acid compounds.

CONCLUSIONMyocardial injuries caused by ISO or I/R injured the structure and function of rat myocardial mitochondria and sarcolemma.

Animals ; Disease Models, Animal ; Male ; Mitochondria, Heart ; pathology ; ultrastructure ; Mitochondrial Membranes ; pathology ; ultrastructure ; Myocardial Reperfusion Injury ; pathology ; Rats ; Rats, Wistar ; Sarcolemma ; pathology ; ultrastructure

OBJECTIVETo investigate the effect of microtubule depolymerization on mitochondria damage in rat myocardiocytes early after hypoxia.

METHODSMyocardiocytes from Wistar rats were isolated according to routine procedure, and they were randomly divided into control group, depolymerization group (with treatment of 4 micromol/L colchicines in the culture medium), hypoxia group, hypoxia and depolymerization group (with treatment of 4 micromol/L colchicines in the culture medium combined with low oxygen tension). The changes in distribution of the mitochondria were examined with laser confocal microscopy, the morphology and the structure of mitochondria was observed by transmission electron microscope, the respiration control ratio (RCR) was determined by respirometer, and the content of adenosine triphosphate (ATP) in endochylema was detected with liquid chromatograph at 20, 30, 60 post-hypoxia minutes (PHM).

RESULTSIn control group, the mitochondria was in granular form, with regular arrangement, while mild changes were observed in depolymerization group. At 20, 30, and 60 PHM, the disarrangement in distribution and morphologic damage were aggravated in hypoxia depolymerization group, and the RCR (1.58 +/- 0.37, 1.51 +/- 0.32, 1.12 +/- 0.11, respectively) were evidently lower than those in hypoxia group (3.85 +/- 0.56, 2.98 +/- 0.44, 1.79 +/- 0.73, respectively, P < 0.01). The content of ATP showed the same tendency at the same time-points (419 +/- 83, 326 +/- 73, 295 +/- 58 ng/mg) compared with hypoxia depolymerization group [(475 +/- 68, 397 +/- 59, 336 +/- 67 ng/mg) in hypoxia group].

CONCLUSIONThe disarrangement in distribution of mitochondria, as well as the damage in mitochondrial structure, respiratory, function and energy metabolism, can be aggravated by microtubule depolymerization after hypoxia, which indicates that microtubule depolymerization plays an important role in the mitochondria damage.

Animals ; Cell Hypoxia ; Cells, Cultured ; Colchicine ; adverse effects ; Disease Models, Animal ; Hypoxia ; pathology ; Microtubules ; pathology ; Mitochondria, Heart ; drug effects ; pathology ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo detect the levels of miR-499 and relative proteins in hearts of mice after exercise training, and investigate the mechanism of exercise-regulative apoptosis.

METHODSMale C57BL/6 mice were randomly divided into 3 groups( n = 14): sedentary (SE), exercise training 1 (ET1) and exercise training 2 (ET2) group. SE did not do any exercise. ET1 performed swimming training for 8 weeks. ET2 performed the same work as ET1 until the 5th week. Then, mice trained twice a day until the end of training. TUNEL assay was applied to test myocardial apoptosis, RT-PCR and Western blot were used to detect miR-499 and proteins levels respectively.

RESULTSCompared with SE, stress in ET1 failed to affect apoptotic index (AI) and miR-499-CaN-Drp-1 pathway (P > 0.05). In contrast, exercise load in ET2 increased miR-499 level, decreased Drp-1 level and AI with statistical significance respectively (P < 0.05), but neither CaN expression nor CaN activity was changed significantly (P > 0.05).

CONCLUSIONSwimming training can inhibit myocardial apoptosis, and the decrease in Drp-l may be responsible for the reduced myocardial apoptosis. CaN, the upstream protein, does not participate in exercise-regulative apoptosis.

Animals ; Apoptosis ; Dynamins ; metabolism ; Heart ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs ; metabolism ; Mitochondria, Heart ; physiology ; Myocardium ; pathology ; Physical Conditioning, Animal ; Swimming

OBJECTIVEOxidative stress and apoptosis play a critical role in the pathogenesis of congestive heart failure (CHF) induced by doxorubicin (Dox) or ischemia/reperfusion. Heat shock protein 27 (Hsp27) could reduce oxidative stress induced apoptosis in various cell types in vitro and attenuate ischemia/reperfusion induced cardiac dysfunction in isolated perfused mouse heart. In this study, we investigated the impact of Hsp27 overexpression on oxidative stress and apoptosis in Dox-induced mice cardiac dysfunction model.

METHODSBoth Hsp27 transgenic mice (TG) and wild type littermates (WT) received a single dosage of Dox (25 mg/kg IP) or saline. On day 3, histological examinations (Paraffin section and HE staining, mitochondria ultrastructure), in situ cardiomyocytes apoptosis assay (TUNEL, immunohistochemistry against alpha-actinin for cardiomyocytes, hoechst33342 for nuclei staining), protein oxidative damage assay (immunoblot against DNP) were performed on cardiac tissue samples. Pleural effusion and histological changes of heart and lung were examined in dead mice.

RESULTS(1) Significant pleural effusion, pulmonary congestion, alveoli collapse and extravasated red blood cells were observed in all died mice. (2) Pronounced cardiomyocyte damages and inhomogeneous HE staining were observed in almost all dead mice except for one TG mouse died at day 4 which showed homogeneous HE staining and only slightly cardiomyocyte damages. (3) Cardiac fibrosis was presented in WT mice but not in TG mice. (4) Dox-induced cardiomyocyte apoptosis and protein carbonylation were significantly attenuated in TG mice compared those in WT mice. (5) Severity of Dox-induced mitochondria damage including increased density, swollen cristae and loss of cristae definition was significantly reduced in TG mice compared to that in WT mice were seen in all the examined myocytes of the LV myocardium samples of Dox-treated mice.

CONCLUSIONHsp27 could attenuate Dox-induced myocardial damage by reducing cardiomyocyte apoptosis, mitochondria damage and protein carbonylation.

Animals ; Apoptosis ; Doxorubicin ; HSP27 Heat-Shock Proteins ; genetics ; Heart Failure ; chemically induced ; physiopathology ; Mice ; Mice, Transgenic ; Mitochondria, Heart ; metabolism ; pathology ; Myocytes, Cardiac ; cytology ; Oxidative Stress ; Protein Carbonylation

OBJECTIVETo investigate the influence of pinacidil preconditioning on the protection of the structure and respiratory function of injured myocardial mitochondria in scalded rats.

METHODSSeventy-five healthy Wistar rats, weighed 250 approximately 300 g, were randomly divided into three groups: i.e. control (n = 9, with intraperitoneal injection of 50 microg/kg isotonic saline), scald (n = 33, with 30% TBSA full thickness scald) and pre-conditioning (n = 33, with same extent of scald injury after intraperitoneal injection of 50 microg/kg pinacidil) groups. Mitochondrial ultrastructure was observed by transmission electron microscope. The mitochondrial respiratory function, the MDA content and the superoxide anion level were determined with corresponding methods.

RESULTSThe degree of injury to rat myocardial mitochondria in pre-conditioning group was less intensive than that in scald group (P < 0.05 or 0.01). The respiratory control rate in pre-conditioning group was obviously higher than that in scald group (P < 0.05), and the contents of MDA and superoxide anion in pre-conditioning group were markedly lower than those in scald group (P < 0.05 or 0.01), as evidenced by their contents at 3 post scalding hours (0.60 +/- 0.09 micromol/g and 0.127 +/- 0.020) were obviously lower than those in scald group (0.83 +/- 0.07 micromol/g and 0.169 +/- 0.015) (P < 0.01).

CONCLUSIONPinacidil preconditioning was beneficial in the protection of myocardial mitochondria in scalded rats, and it might be related to the pre-opening of potassium channel which was sensitive to mitochondrial ATP.

Animals ; Burns ; drug therapy ; metabolism ; pathology ; Cell Respiration ; drug effects ; Disease Models, Animal ; Mitochondria, Heart ; metabolism ; pathology ; Pinacidil ; therapeutic use ; Rats ; Rats, Wistar ; Superoxides ; analysis

BACKGROUNDMyocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats.

METHODSSeventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection. Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy. In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis. Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage. Oxidative stress was assessed by mitochondrial lipid and protein oxidation, and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity.

RESULTSSepsis-induced inflammatory cell infiltration, myocardium degeneration and dropsy were time-dependent. Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge. Compared with sham-treated rats, the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours, 12 hours and 24 hours post-injection (P < 0.05). The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis, indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B. Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner. Both superoxide dismutase and glutathione peroxidase activities decreased, while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge.

CONCLUSIONSSeptic challenge induced myocardial apoptosis and mitochondrial damage. Furthermore, mitochondrial damage via alteration of defenses against reactive oxygen species might play an important role in myocardial apoptosis during sepsis.

Animals ; Apoptosis ; physiology ; Male ; Mitochondria, Heart ; metabolism ; pathology ; Myocardium ; metabolism ; pathology ; Oxidative Stress ; physiology ; Rats ; Rats, Sprague-Dawley ; Sepsis ; metabolism ; physiopathology