Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype.
Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype.
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DOI：
10.1161/jaha.118.009112
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发表时间：
2018-09-18
影响因子：
5.4
通讯作者：
Lakatta EG
中科院分区：
文献类型：
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作者：
Wang M;Zhang L;Zhu W;Zhang J;Kim SH;Wang Y;Ni L;Telljohann R;Monticone RE;McGraw K;Liu L;de Cabo R;Lakatta EG
衰老指数增加典型心血管疾病的发病率和死亡率，主要是由于动脉壁内分子、细胞和组织水平的动脉促炎性变化。大鼠的热量限制（CR）改善了动脉功能，延长了健康寿命和寿命。然而，CR如何影响大鼠动脉壁内分子、细胞和组织表型变化的促炎景观仍有待阐明。从幼龄（6月龄）和老龄（24月龄）Fischer 344大鼠中采集主动脉，自由进食，第二组从1月龄开始维持40% CR。动脉壁的组织学和形态学分析表明，CR显著减少了动脉壁内年龄相关的内膜中层增厚、胶原沉积和弹性蛋白分级/降解。免疫染色/印迹显示，CR可有效防止动脉壁中血小板源性生长因子密度、基质金属蛋白酶II型活性、转化生长因子β 1及其下游信号分子（针对十肢瘫痪同源物2/3（p-SMAD-2/3）的磷酸化母体）的年龄相关性增加。在从AL和CR大鼠直肠分离的早期传代培养的血管平滑肌细胞中，CR缓解了年龄相关的血管平滑肌细胞表型变化、促纤维化信号传导和血小板源性生长因子应答的迁移/增殖。 CR减少与主动脉壁内发生的老化相关的基质和细胞促炎症，这些炎症可归因于血小板衍生生长因子信号传导。因此，CR减少了血小板源性生长因子相关的信号级联，有助于延缓生物老化和保存更年轻的主动脉壁表型。
Aging exponentially increases the incidence of morbidity and mortality of quintessential cardiovascular disease mainly due to arterial proinflammatory shifts at the molecular, cellular, and tissue levels within the arterial wall. Calorie restriction (CR) in rats improves arterial function and extends both health span and life span. How CR affects the proinflammatory landscape of molecular, cellular, and tissue phenotypic shifts within the arterial wall in rats, however, remains to be elucidated. Aortae were harvested from young (6‐month‐old) and old (24‐month‐old) Fischer 344 rats, fed ad libitum and a second group maintained on a 40% CR beginning at 1 month of age. Histopathologic and morphometric analysis of the arterial wall demonstrated that CR markedly reduced age‐associated intimal medial thickening, collagen deposition, and elastin fractionation/degradation within the arterial walls. Immunostaining/blotting showed that CR effectively prevented an age‐associated increase in the density of platelet‐derived growth factor, matrix metalloproteinase type II activity, and transforming growth factor beta 1 and its downstream signaling molecules, phospho‐mothers against decapentaplegic homolog‐2/3 (p‐SMAD‐2/3) in the arterial wall. In early passage cultured vascular smooth muscle cells isolated from AL and CR rat aortae, CR alleviated the age‐associated vascular smooth muscle cell phenotypic shifts, profibrogenic signaling, and migration/proliferation in response to platelet‐derived growth factor. CR reduces matrix and cellular proinflammation associated with aging that occurs within the aortic wall and that are attributable to platelet‐derived growth factor signaling. Thus, CR reduces the platelet‐derived growth factor–associated signaling cascade, contributing to the postponement of biological aging and preservation of a more youthful aortic wall phenotype.