Pathophysiology of vascular calcification: Pivotal role of cellular senescence in vascular smooth muscle cells.
The accumulation of senescent cells within tissues can potentially lead to biological dysfunction and manifestation of disease associated with ageing. The majority of senescent cells display a commonly altered secretome similar to a wound healing response (termed the senescence-associated secretory phenotype or SASP), which could have deleterious implications on the tissue microenvironment. However, senescent cells also appear to have a cell-type (or even cell-strain) exclusive senescent phenotype (CESP), an area of research that is underexplored. One such CESP is the pro-calcificatory phenotype recently reported in senescent vascular smooth muscle cells (VSMCs). Senescent VSMCs have been shown to overexpress genes and proteins (including RUNX-2, alkaline phosphatase (ALP), type I collagen and BMP-2) associated with osteoblasts, leading to partial osteoblastic transdifferentiation. As such, it has been suggested that senescent VSMCs contribute to cardiovascular dysfunction through induction of vascular calcification. This review discusses recent findings on VSMC senescence and their potential role in the pathophysiology of vascular calcification.
Burton
D G A
DG
Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Miami, Miami, FL 33125, USA. dburton@med.miami.edu
Matsubara
H
H
Ikeda
K
K
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002114:Calcinosis / Q000503:physiopathology*; D016922:Cellular Senescence; D024042:Collagen Type I / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle; D010641:Phenotype; D015854:Up-Regulation; D014652:Vascular Diseases / Q000503:physiopathology*
D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D000469:Alkaline Phosphatase