Abstract

Vascular aging predisposes the elderly to the progression of many aging-related vascular disorders and leads to deterioration of cardiovascular diseases (CVD). However, the underlying mechanisms have not been clearly elucidated. Agonistic autoantibodies against angiotensin II type 1 (AT1) receptor (AT1-AAs) have been demonstrated to be pro-inflammatory and contribute to the progression of atherosclerosis. However, the association between AT1-AAs and vascular aging has not been defined. Peripheral arterial disease (PAD) is an acknowledged vascular aging-related disease. In this study, AT1-AAs were detected in the sera of patients with PAD and the positive rate was 44.44% (n=63) vs. 17.46% in non-PAD volunteers (n=63). In addition, case-control analysis showed that AT1-AAs level was positively correlated with PAD. To reveal the causal relationship between AT1-AAs and vascular aging, an AT1-AAs-positive rat model was established by active immunization. The carotid pulse wave velocity was higher, and the aortic endothelium-dependent vasodilatation was attenuated significantly in the immunized rats. Morphological staining showed thickening of the aortic wall. Histological examination showed that levels of the senescent markers were increased in the aortic tissue, mostly located at the endothelium. In addition, purified AT1-AAs-IgGs from both the immunized rats and PAD patients induced premature senescence in cultured human umbilical vein endothelial cells. These effects were significantly blocked by the AT1 receptor blocker. Taken together, our study demonstrates that AT1-AAs contribute to the progression of vascular aging and induce EC senescence through AT1 receptor. AT1-AA is a novel biomarker of vascular aging and aging-related CVD that acts to accelerate EC senescence.

Highlights

  • Vascular aging is a dominant risk factor for many agingrelated cardiovascular diseases (CVD), represented by atherosclerosis, coronary artery disease, vascular calcification, hypertension and stroke [1]

  • AAs with vascular aging-related diseases, we collected sera from 63 peripheral arterial disease (PAD) patients recruited from Beijing Anzhen hospital and determined the level of angiotensin II (Ang II) type 1 (AT1)-AAs

  • The main findings of our research are (1) a high serum AT1-AAs level was closely associated with PAD; (2) long-term exposure to AT1-AAs could induce vascular aging and endothelial cells (ECs) senescence in vivo; (3) AT1-AAs-IgGs induced EC senescence in an AT1 receptor-dependent pathway

Read more

Summary

Introduction

Vascular aging is a dominant risk factor for many agingrelated cardiovascular diseases (CVD), represented by atherosclerosis, coronary artery disease, vascular calcification, hypertension and stroke [1]. AT1-AAs induce vascular aging aging is characterized by endothelial dysfunction, which is associated with decreased endothelium-dependent relaxation during aging in humans [3]. Stiffening of large elastic arteries is recognized as another key vascular change associated with the development of endothelial dysfunction during aging [4, 5]. Whether AT1-AAs can induce vascular aging or EC senescence has never been explored. To address this issue, we performed a case-control study to explore the association between serum AT1-AAs levels and peripheral arterial disease (PAD). We conducted in vivo experiments with the use of AT1-AAspositive rat models to explore the role of AT1-AAs in inducing vascular aging. We performed in vitro experiments to investigate the effect of AT1-AAs on EC senescence and the underlying mechanism

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call