APOPTOSIS IN TARGET ORGANS OF HYPERTENSION
APOPTOSIS IN TARGET ORGANS OF HYPERTENSION
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DOI：
10.1161/01.hyp.26.4.642
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发表时间：
1995-10-01
期刊：
影响因子：
8.3
通讯作者：
TREMBLAY, J
中科院分区：
文献类型：
--
作者：
HAMET, P;RICHARD, L;TREMBLAY, J
细胞凋亡或程序性细胞死亡通常与细胞增殖和分化异常有关。由于高血压影响的器官发生肥大/增生或重塑，我们在遗传性高血压小鼠和大鼠以及培养的血管平滑肌细胞中原位评估了心脏、肾脏和大脑的细胞凋亡程度。细胞凋亡的特征表现为形态学特征、DNA片段和阶梯状，以及提取DNA和组织切片的3' OH末端脱氧核苷酸转移酶标记。本报告首次提供了遗传性高血压大鼠和小鼠品系全器官细胞凋亡增加的证据：在自发性高血压大鼠（SHR）的心脏和自发性高血压小鼠的心脏（心室心肌细胞）、肾脏（内皮层和髓质）和大脑（皮层、纹状体、海马和丘脑）中，凋亡诱导剂在培养的SHR来源的主动脉平滑肌细胞中作用更高。在血管平滑肌细胞中观察到两种已知的凋亡过程，寡核体分裂和大DNA断裂，但只有前者似乎在SHR中增加。这项研究强调了细胞死亡失调在高血压中的重要性，为研究高血压的发病机制开辟了新的途径，并提出了新的治疗干预靶点。
Apoptosis or programmed cell death frequently parallels abnormalities in cell proliferation and differention. As hypertrophy/hyperplasia or remodeling occurs in organs affected by hypertension, we evaluated the degree of apoptosis in the heart, kidney, and brain in situ in genetically hypertensive mice and rats as well as in cultured vascular smooth muscle cells. Apoptosis was characterized by morphological features, DNA fragmentation, and laddering as well as by terminal deoxynucleotidyl transferase labeling of the 3' OH ends of both extracted DNA and tissue sections. The present report provides the first evidence of increased apoptosis in whole organs of genetically hypertensive rat and mouse strains: in the heart of spontaneously hypertensive rats (SHR) and in the heart (ventricular cardiomyocytes), kidney (inner cortex and medulla), and brain (cortex, striatum, hippocampus, and thalamus) of spontaneously hypertensive mice, with a higher effect of apoptotic inducers in cultured aortic smooth muscle cells derived from SHR. Both types of known apoptotic processes, oligonucleosomal cleavage and large DNA fragmentation, were observed in vascular smooth muscle cells, but only the former appeared to be increased in SHR. This study underlines the importance of cell death dysregulation in hypertension, reveals a new route for investigation of the pathogenesis of hypertension, and suggests novel targets of therapeutic intervention.