Table 3 Senescent cell types, associated markers, and mechanisms of action in cardiomyopathy.
From: The role of cellular senescence in cardiovascular disease
Research model | Cellular senescence types | Targets or pathways | Mechanism of action | Effects | Refs |
|---|---|---|---|---|---|
Diabetic cardiomyopathy | Cardiomyocyte | SA-β-gal, p16INK4a, p53, | • OP treatment downregulates CDK1, GTSE1, and CCNB2 transcriptional expressions. • Inhibition of p53 prevents Cardiac Aging by improving glucose metabolism and angiogenesis through increased HIF-1α protein stability. • D + Q treatment efficiently eliminated senescent cells, rescuing CSCs function, which resulted in functional myocardial repair/regeneration. | Alleviate | |
Adriamycin cardiomyopathy | Cardiomyocyte cardiac progenitor cells | p53, p16, p21, DDR, SA-β-gal, Telomere shortening, SASP | • PARP-2 inhibits the expression and activity of SIRT1. • C5aRA downregulates levels of p53, p16, p21. • The pro-survival miR-34a upregulates the expression of its target genes Bcl-2 and SIRT1, and downregulates the acetylation level of p53 and the expression level of p16INK4a. • Doxorubicin increased the relative proportion of p16INK4a+/myosin+ cells at the expense of the p16INK4a−/myosin+ as well as increased SA-β-gal activity in the left ventricle. • Senolytics can effectively reverse the aging phenotype associated with hCardioids by reducing oxidative stress, aging biomarkers, and SASP, thereby restoring organoid viability, function, cardiac progenitor cell numbers, and cardiomyocyte proliferation capacity. • Knocking down p16INK4A in hCPCs can activate anti-apoptotic and antioxidant pathways via the NF-κB signaling pathway to reverse their senescent phenotype and exert antioxidant effects on aged hCPCs. | Alleviate | |
Dilated cardiomyopathy | Myofibroblasts cardiomyocyte | p53, SA-β-gal, Telomere shortening, Mitochondrial dysfunction | • Deletion of the Lmna gene in fibroblasts may result in LMNA-associated DCM by inducing double-stranded DNA breaks, activating the DDR pathway, and inducing SASP protein expression. • In vitro, sST2 activated TGFβ signaling through the phosphorylation of the SMAD complex to induce MCF activation and inhibit cellular senescence by the Sirt1/p53/p21 signaling pathway. • Active MnSOD detoxification activity, lacking the normal switch between non-acetylated and acetylated forms, dysregulates mitochondrial physiology during development. • Telomere erosion, cellular senescence, and death characterize aged diseased hearts and the development of cardiac failure in humans. • Changes in sFRP-1 expression during cellular senescence may influence the function of cardiac fibroblasts by affecting the Wnt signaling pathway. | Promote | |
Arrhythmogenic cardiomyopathy | Fibroblasts | SASP, DDR, SAHF | Mutant LEMD2 leads to remarkable changes in the shape of nuclei with condensed heterochromatin formation, reduced proliferation capacity, and cell senescence in fibroblasts, suggesting the involvement of LEMD2 in chromatin remodeling and premature aging. | Promote | [196] |
