Schipke Julia, Grimm Clara, Arnstein Georg, Kockskämper Jens, Sedej Simon, Mühlfeld Christian
Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Division of Cardiology, Medical University of Graz, Graz, Austria.
J Anat. 2016 Jul;229(1):75-81. doi: 10.1111/joa.12463. Epub 2016 Mar 17.
Left ventricular (LV) hypertrophy in response to hypertension and increased afterload frequently progresses to heart failure. It is under debate whether the loss of cardiomyocytes contributes to this transition. To address this question, female C57BL/6 wild-type mice were subjected to transverse aortic constriction (TAC) and developed compensated LV hypertrophy after 1 week, which progressed to heart failure characterized by reduced ejection fraction and pulmonary congestion 4 weeks post-TAC. Quantitative, design-based stereology methods were used to estimate number and mean volume of LV cardiomyocytes. DNA strand breaks were visualized using the TUNEL method 6 weeks post-TAC to quantify the number of apoptotic cell nuclei. The volume of the LV myocardium as well as the cardiomyocyte mean volume increased progressively after TAC. In contrast, the number of LV cardiomyocytes remained constant 1 and 4 weeks post-TAC in comparison to sham-operated mice. Moreover, there was no significant difference in the number of cardiomyocyte nuclei stained for DNA strand breaks at 6 weeks post-TAC. It was concluded that the loss of cardiomyocytes is not required for the transition from compensated hypertrophy to heart failure induced by TAC in the female murine heart.
高血压和后负荷增加引起的左心室(LV)肥厚常常进展为心力衰竭。心肌细胞的丢失是否促成了这种转变仍存在争议。为解决这个问题,对雌性C57BL/6野生型小鼠进行了主动脉缩窄(TAC),1周后出现代偿性LV肥厚,并在TAC后4周进展为以射血分数降低和肺淤血为特征的心力衰竭。采用基于设计的定量体视学方法估计LV心肌细胞的数量和平均体积。在TAC后6周使用TUNEL法观察DNA链断裂情况,以量化凋亡细胞核的数量。TAC后LV心肌的体积以及心肌细胞平均体积逐渐增加。相比之下,与假手术小鼠相比,TAC后1周和4周LV心肌细胞数量保持不变。此外,TAC后6周,DNA链断裂染色的心肌细胞核数量没有显著差异。得出的结论是,在雌性小鼠心脏中,TAC诱导的从代偿性肥厚转变为心力衰竭并不需要心肌细胞的丢失。