Abstract
Age-related functional decline is a physiological phenomenon that occurs in all organ systems. However, the acceleration and early occurrence of this process are observed in cardiovascular pathologies, including hypertension. This study aimed to investigate SIRT1–PTEN signaling in aortic tissue from spontaneously hypertensive rats (SHRs) and changes in SIRT1 and PTEN expression following treatment with Pinggan-Qianyang decoction (PGQYD) and explore the mechanism involved in the treatment of hypertensive vascular aging with traditional Chinese medicine. In this study, we used two rat models: spontaneously hypertensive rats (SHRs) at 14 and 64 weeks of age and WKY rats at 64 weeks of age. The degree of irritability and rotation tolerance time were evaluated to determine the effects of PGQYD on animal behavior. The morphology of the thoracic aorta was examined by hematoxylin-eosin (HE) and Masson staining and electron microscopy. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and superoxide dismutase (SOD) and anti-superoxide anion content were detected. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to observe the thoracic aorta during vascular aging. RT-qPCR, immunofluorescence, and Western blot analysis were performed to detect changes in the mRNA and protein expression of p53, p21, SIRT1, and PTEN in rat aortic tissues. Behavioral tests and histological and morphological analyses showed the remarkable amelioration of vascular aging after PGQYD treatment compared with that in the older SHRs. Moreover, PGQYD significantly decreased vascular aging in SHRs, as indicated by reduced SA-β-Gal staining, NADPH oxidase activity, and p53 and p21 expression, and increased anti-superoxide anion and SOD content. Furthermore, PGQYD increased SIRT1 and PTEN expression, but the downregulated expression of SIRT1 induced by a SIRT1 inhibitor abolished the PGQYD-induced antiaging effects on gene expression and antioxidant activity and enhanced PTEN expression. PGQYD could ameliorate vascular aging effects in SHRs, which may have been mediated via the regulation of SIRT1–PTEN signaling in aortic tissue.
Highlights
The aging of vascular smooth muscle cells (VSMCs) is the main pathological mechanism underlying cardiovascular and cerebrovascular diseases, such as vascular aging, hypertension, and atherosclerosis [1]
Compared with the Old group, the TCM group showed a significant decrease in the degree of irritability (P < 0.05) and markedly prolonged rotation tolerance time (P < 0.05), qualities that are essentially consistent with the clinical manifestations of liverYang hyperactivity syndrome in traditional Chinese medicine
These results demonstrated that Pinggan-Qianyang decoction (PGQYD) could improve the behavior of the spontaneously hypertensive rats (SHRs)
Summary
The aging of vascular smooth muscle cells (VSMCs) is the main pathological mechanism underlying cardiovascular and cerebrovascular diseases, such as vascular aging, hypertension, and atherosclerosis [1]. Senescent VSMCs can change the local tissue microenvironment, promoting the occurrence of inflammation and vascular sclerosis [2] and aggravating the development of atherosclerosis and hypertension, by secreting a variety of cytokines and growth factors. In addition to its activity against histones as substrates, SIRT1 can interact with a variety of transcription factors including p53, FOXO1, STAT3, PGC-1α, and PTEN to regulate their transcriptional regulation activity [5]. Of these transcription factors, PTEN, one of the earliest identified tumor suppressor genes with phosphatase activity, is related to the regulation of various physiological activities and processes, such as the cell cycle, apoptosis, adhesion, migration, and vascular growth [6]. PTEN can both inhibit the proliferation and migration of VSMCs and promote VSMC apoptosis [7]
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