Remodeling of Cardiomyocytes: Study of Morphological Cellular Changes Preceding Symptomatic Ischemic Heart Failure (original) (raw)
Related papers
Cardiomyocyte remodeling in ischemic heart disease
Medicina ( …, 2008
Objective. The aim of the study was to detect changes in left ventricular cardiomyocyte size and shape in response to chronic ischemia and loss of cardiac tissue (myocardial infarction) during the course of ischemic heart disease (IHD).
Structural remodeling of cardiac myocytes in patients with ischemic cardiomyopathy
Circulation, 1992
BACKGROUND Chronic ischemic heart disease may lead to ventricular dilation and congestive heart failure (ischemic cardiomyopathy [ICM]). The changes in cardiac myocyte shape associated with this dilation, however, are not known. METHODS AND RESULTS Left ventricular myocyte dimensions were assessed in cells isolated from explanted human hearts obtained from patients with ICM (n = 6) who were undergoing heart transplantation. Cells were also examined from three nonfailing donor hearts with normal coronary arteries (NCA). Compared with cells from patients with NCA, myocyte length was 40% longer in hearts from patients with ICM (197 +/- 8 versus 141 +/- 9 microns, p less than 0.01), cell width was not significantly different, and cell length/width ratio was 49% greater (11.2 +/- 0.9 versus 7.5 +/- 0.6, p less than 0.01). Sarcomere length was the same in myocytes from both groups. The extent of myocyte lengthening is comparable to the increase in end-diastolic diameter commonly reported ...
Cytometry Part A, 2019
Ischemic lesions of the heart, including myocardial infarction, are the most common pathologies of human cardiovascular system. Despite all the research and achievements of medicine in this field, the mortality from this disease remains heavy. Therefore, studying of processes occurring in the myocardium in the early and late postinfarction periods remains important. Rat left ventricular cardiomyocyte (CMC) ploidy, hypertrophy, hyperplasia, and ultrastructure were investigated in 2, 6, and 26 weeks after experimental myocardial infarction, caused by permanent ligation of left coronary artery. Cytofluorimetric study of CMC ploidy revealed no difference between normal, sham-operated, and infarcted animals for all the tested stages. However, interference microscopy indicated significant changes in cells size. CMC dry mass of infarcted rats in 2 weeks after surgery was 1.5 times lower than in control and sham operated groups. Electron microscopy analysis of CMC revealed disruption of sarcomere structure. However, in 6 weeks after surgery CMC dry mass was 1.6 times higher than in control. In 26 weeks after myocardial infarction CMC dry mass exceeded control only in peri-infarction zone. Cell counting showed that the number of left ventricular CMC, reduced as a result of myocardial infarction, was not restored during myocardial remodeling.
Histological remodeling in an ovine heart failure model resembles human ischemic cardiomyopathy
Cardiovascular …, 2001
Staged coronary embolization, causing myocardial microinfarctions, has been shown in dogs and sheep to cause chronic ischemic heart failure (HF) that resembles the hemodynamics of the human condition. However, its histopathological basis remains unclear. We examined the hypothesis that the ventricular remodeling seen in such sheep resembles the histopathology of human ischemic cardiomyopathy (ICM). Understanding the pathophysiology of this model will determine its place in the development of treatment strategies for HF. Global left ventricular (LV) damage resulting in HF was induced by staged coronary embolization in 11 sheep. Six others served as controls (normal control, NC). In HF sheep, the heart was harvested 6 months after LV ejection fraction (EF) had stabilized at < 35%. Histopathological profiles were compared in biventricular transverse sections at midpapillary level using computed image analysis. LV end-diastolic volume increased in the HF group from 84.9 29 to 122.4 30.3 ml (n = 11, P < .05), but myocytes across the LV wall in noninfarcted zones decreased (435.7 38.2 NC; 297.8 48.4/unit area HF; n = 11, P < .0001) as did myocyte nuclear density (990.5 51.5 NC; 677.5 121.1/ mm 2 HF, n = 11, P < .0001). In contrast, LV replacement and interstitial fibrosis increased as did myocyte diameter in noninfarcted zones: 0.1 0.1 to 6.2 4.5% (P =.0049); 2.0 1.0 to 7.6 4.9% (P =.0149); and 10.0 0.5 to 15.9 2.2 mm (P < .0001), respectively. Although LV myocyte nuclear length increased (10.2 1.0 NC; 12.2 0.9 mm HF, n = 11, P =.0006), right ventricular (RV) myocyte nuclear density and length did not alter. In this ovine chronic HF model, LV dilation and interstitial and myocyte remodeling resemble human ICM.
Structural remodelling of cardiomyocytes in the border zone of infarcted rabbit heart
Molecular and Cellular Biochemistry, 2007
Cardiomyocyte dedifferentiation, as detected in hibernating myocardium of chronic ischemic patients, is one of the characteristics seen at the border of myocardial infarcts in small and large animals. Our objectives were to study in detail the morphological changes occurring at the border zone of a rabbit myocardial infarction and its use as model for hibernating myocardium. Ligation of the left coronary artery (LAD) was performed on rabbit hearts and animals were sacrificed at 2, 4, 8 and 12 weeks postinfarction. These hearts together with a non-infarcted control heart were perfusion-fixed and tissue samples were embedded in epoxy resin. Hibernating cardiomyocytes were mainly distributed in the non-infarcted region adjacent to the border zone of infarcted myocardium but only in a limited number. In the border zone itself vacuolated cardiomyocytes surrounded by fibrotic tissue were frequently observed. Ultrastructural analysis of these vacuolated cells revealed the presence of a basal lamina inside the vacuoles adjacent to the surrounding membrane, the presence of pinocytotic vesicles and an association with cisternae of the sarcoplasmatic reticulum. Myocyte quantitative analyses revealed a gradual increase in vacuolar area/total cell area ratio and in collagen fibril deposition inside the vacuoles from 2 to 12 weeks post-infarction. Related to the remote zone, the increase in cell width of myocytes located in and adjacent to the border zone demonstrated cellular hypertrophy. These results indicate the occurrence of cardiomyocyte remodelling mechanisms in the border zone and adjacent regions of infarcted myocardium. It is suggested that the vacuoles represent plasma membrane invaginations and/or dilatations of T-tubular structures.
Circulation, 2017
Background -Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACM) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI). We aim to understand the process and regulation of ACM proliferation and its role in new cardiomyocyte formation of post-MI mouse hearts. Methods -β-actin-GFP transgenic mice and fate-mapping Myh6-MerCreMer-tdTomato/lacZ mice were used to trace the fate of ACMs. In a co-culture system with neonatal rat ventricular myocytes (NRVMs), ACM proliferation was documented with clear evidence of cytokinesis observed with time-lapse imaging. Cardiomyocyte proliferation in the adult mouse post-MI heart was detected by cell cycle markers and EdU incorporation analysis. Echocardiography was used to measure cardiac function and histology was performed to determine infarction...
Cardiomyocyte substructure reverts to an immature phenotype during heart failure
The Journal of Physiology
As reactivation of the fetal gene program has been implicated in pathological remodelling during heart failure (HF), we examined whether cardiomyocyte subcellular structure and function revert to an immature phenotype during this disease. r Surface and internal membrane structures appeared gradually during development, and returned to a juvenile state during HF. Similarly, dyadic junctions between the cell membrane and sarcoplasmic reticulum were progressively 'packed' with L-type Ca 2+ channels and ryanodine receptors during development, and 'unpacked' during HF. r Despite similarities in subcellular structure, dyads were observed to be functional from early developmental stages, but exhibited an impaired ability to release Ca 2+ in failing cardiomyocytes. r Thus, while immature and failing cardiomyocytes share similarities in subcellular structure, these do not fully account for the marked impairment of Ca 2+ homeostasis observed in HF.