Targeting Molecular Mechanism of Vascular Smooth Muscle Senescence Induced by Angiotensin II, A Potential Therapy via Senolytics and Senomorphics

• Published in: International journal of molecular sciences Vol. 21; no. 18; p. 6579
• Main Authors: Okuno, Keisuke, Cicalese, Stephanie, Elliott, Katherine J, Kawai, Tatsuo, Hashimoto, Tomoki, Eguchi, Satoru
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.09.2020; MDPI
• Subjects: Age; Aging; Aging - physiology; Angiotensin; Angiotensin II; Angiotensin II - physiology; Animals; Apoptosis; Atherosclerosis; Cardiovascular diseases; Cardiovascular Diseases - prevention & control; Cellular Senescence; Chronic illnesses; Cyclin-dependent kinases; Deoxyribonucleic acid; DNA; Endoplasmic reticulum; Fibroblasts; Heart failure; Humans; Inflammation; Kinases; Low density lipoprotein receptors; Lymphocytes; Metabolism; Mitochondria; Molecular modelling; Molecular Targeted Therapy; Muscles; Myocytes, Smooth Muscle - physiology; Oxidative stress; Proteins; Renin-Angiotensin System; Review; Risk analysis; Risk factors; Senescence; senolytic; Smooth muscle; Stiffness; vascular smooth muscle cells; senolytic; aging; vascular smooth muscle cells; angiotensin II
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21186579

Cardiovascular disease (CVD) is a prevalent issue in the global aging population. Premature vascular aging such as elevated arterial stiffness appears to be a major risk factor for CVD. Vascular smooth muscle cells (VSMCs) are one of the essential parts of arterial pathology and prone to stress-induced senescence. The pervasiveness of senescent VSMCs in the vasculature increases with age and can be further expedited by various stressing events such as oxidative stress, mitochondria dysfunction, endoplasmic reticulum stress, and chronic inflammation. Angiotensin II (AngII) can induce many of these responses in VSMCs and is thus considered a key regulator of VSMC senescence associated with CVD. Understanding the precise mechanisms and consequences of senescent cell accumulation may uncover a new generation of therapies including senolytic and senomorphic compounds against CVD. Accordingly, in this review article, we discuss potential molecular mechanisms of VSMC senescence such as those induced by AngII and the therapeutic manipulations of senescence to control age-related CVD and associated conditions such as by senolytic.