Jovanovic S, Grantham A J, Tarara J E, Burnett J C, Jovanovic A, Terzic A
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Int J Mol Med. 1999 Feb;3(2):153-5. doi: 10.3892/ijmm.3.2.153.
Based on positive identification of DNA replication and mitotic division in cardiomyocytes isolated from failing hearts, it has been proposed that adult ventricular cardiomyocytes can gain the capacity to proliferate with progression of heart failure. However, due to the lack of a reliable method to distinctly image individual cardiac cells within the myocardial syntitium, such a concept still remains largely controversial. In the present study, we used laser confocal microscopy, to image cross-sections of intact myocardium stained with fluorescein-conjugated wheat germ agglutinin and propidium iodide. This approach allowed to clearly separate the profile of individual myocytes within cardiac tissue sections. We found that in the left ventricles of dogs, subjected to tachycardia-induced cardiomyopathy, the number of cells was significantly increased in both longitudinal and transversal sections. Treatment with the angiotensin-converting enzyme inhibitor, enalapril, reversed these changes to values similar to those found in controls. Therefore, this study provides evidence, at the in situ level, for cellular hyperplasia in heart failure. This supports the more general notion that adult cardiomyocytes may not be terminally differentiated, and that an increase in cell number could contribute to the increase in left ventricular mass observed with progression of disease.
基于对从衰竭心脏分离出的心肌细胞中DNA复制和有丝分裂的阳性鉴定,有人提出成年心室心肌细胞可随着心力衰竭的进展获得增殖能力。然而,由于缺乏一种可靠的方法来清晰地成像心肌合胞体内的单个心肌细胞,这一概念在很大程度上仍存在争议。在本研究中,我们使用激光共聚焦显微镜对用荧光素偶联的麦胚凝集素和碘化丙啶染色的完整心肌的横截面进行成像。这种方法能够清晰地分离心脏组织切片内单个心肌细胞的轮廓。我们发现,在因心动过速诱导心肌病的犬类左心室中,纵向和横向切片中的细胞数量均显著增加。用血管紧张素转换酶抑制剂依那普利治疗可将这些变化逆转至与对照组相似的值。因此,本研究在原位水平上为心力衰竭中的细胞增生提供了证据。这支持了更普遍的观点,即成年心肌细胞可能并非终末分化,并且细胞数量的增加可能导致随着疾病进展观察到的左心室质量增加。