TEMPORAL DIFFERENCES IN FIBROBLAST PROLIFERATION AND PHENOTYPE EXPRESSION IN RESPONSE TO CHRONIC ADMINISTRATION OF ANGIOTENSIN-II OR ALDOSTERONE
TEMPORAL DIFFERENCES IN FIBROBLAST PROLIFERATION AND PHENOTYPE EXPRESSION IN RESPONSE TO CHRONIC ADMINISTRATION OF ANGIOTENSIN-II OR ALDOSTERONE
复制标题
DOI：
10.1016/s0022-2828(95)90359-3
复制
发表时间：
1995-08-01
影响因子：
5
通讯作者：
WEBER, KT
中科院分区：
文献类型：
--
作者：
CAMPBELL, SE;JANICKI, JS;WEBER, KT
循环肾素-血管紧张素-醛固酮系统（RAAS）的慢性激活，如单侧肾缺血（URI）时可能发生的，与左右心室的不良结构重构相关，其特征是修复性（即显微镜下的疤痕）和反应性（即血管周围/间质）纤维化。这些事件的时间进程和参与成纤维期和成纤维期的细胞尚不清楚。在8周的时间里，我们对注射血管紧张素II或醛固酮的大鼠的心脏进行了检查，并与URI大鼠进行了比较。同一心脏组织切片用苏木精和伊红染色，胶原特异性小sirius红染色，或用PCNA或α平滑肌肌动蛋白抗体免疫标记。血管紧张素II或肾缺血时，成纤维细胞增殖表现为肌细胞坏死部位和广泛的血管周围部位的局灶性积聚，在第2天和第4天出现在每个心室，但此后就没有了。含有α -平滑肌肌动蛋白的细胞（肌成纤维细胞）在第2天出现，并持续到肾缺血的第2周和血管紧张素II的第6周。在肾缺血第2 ~ 4天，在坏死部位短暂发现巨噬细胞、中性粒细胞和淋巴细胞。从第2天到第6周，agi诱导的坏死部位以巨噬细胞和淋巴细胞为特征，第2-4天以中性粒细胞为特征。在第14天，两个心室的胶原体积分数明显增加，表现为与成纤维细胞簇和间质/血管周围纤维化相关的未成熟疤痕。相反，在醛固酮输注期间，两个心室的成纤维细胞增殖直到第3周才出现，并且早在第4周就与随后的修复性和反应性纤维化相关，肌成纤维细胞在3-6周之间变得明显；3-8周可见巨噬细胞和淋巴细胞。在醛固酮的任何时间点均未见中性粒细胞。因此，与血管紧张素II和/或醛固酮慢性升高相关的时间细胞反应和心肌纤维化的表现不同。我们得出结论，不同的致病机制与RAAS的这些效应激素有关。1995学术出版社有限公司
Chronic activation of the circulating renin-angiotensin-aldosterone system (RAAS), as can occur with unilateral renal ischemia (URI), is associated with an adverse structural remodeling of the right and left ventricles characterized by reparative (i.e., microscopic scars) and reactive (i.e., perivascular/interstitial) fibrosis. The time course and cells involved in fibroplastic and fibrogenic phases of these events are unclear. Hearts were examined over the course of 8 weeks in rats infused with either angiotensin II or aldosterone, and compared to rats with URI. Tissue sections from the same heart were stained with hematoxylin and eosin, collagen specific picrosirius red, or immunolabeled with PCNA or alpha smooth muscle actin antibody. With angiotensin II or renal ischemia, fibroblast proliferation presenting as focal accumulations at both sites of myocyte necrosis and widespread perivascular locations, was present in each ventricle on days 2 and 4, but not thereafter. alpha-Smooth muscle actin containing cells (myofibroblasts) appeared at day 2 and persisted through week 2 with renal ischemia and week 6 with angiotensin II. Macrophages, neutrophils and lymphocytes were transiently found at sites of necrosis between day 2-4 of renal ischemia. AgII-induced necrotic sites were characterized by macrophages and lymphocytes from day 2 through week 6, and neutrophils at day 2-4. Increased collagen volume fraction, presenting as immature scars associated with fibroblast clusters and interstitial/perivascular fibrosis, was evident on day 14 in both ventricles. In contrast, fibroblast proliferation during aldosterone infusion did not appear in both Ventricles until week 3 and was associated with a subsequent reparative and reactive fibrosis as early as 4 weeks, Myofibroblasts became evident between 3-6 weeks; macrophages and lymphocytes were seen between 3-8 weeks. Neutrophils were not seen at any time point with aldosterone. Thus, the temporal cellular response and appearance of myocardial fibrosis associated with chronic elevations in angiotensin II and/or aldosterone differ. We conclude that separate pathogenic mechanisms are operative with these effector hormones of the RAAS. (C) 1995 Academic Press Limited.