Extracellular matrix roles in cardiorenal fibrosis: Potential therapeutic targets for CVD and CKD in the elderly

Whereas hypertension, diabetes, and dyslipidemia are age-related risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD), aging alone is an independent risk factor. With advancing age, the heart and kidney gradually but significantly undergo inflammation and subsequent fibrosis, which eventually results in an irreversible decline in organ physiology. Through cardiorenal network interactions, cardiac dysfunction leads to and responds to renal injury, and both facilitate aging effects. Thus, a comprehensive strategy is needed to evaluate the cardiorenal aging network. Common hallmarks shared across systems include extracellular matrix (ECM) accumulation, along with upregulation of matrix metalloproteinases (MMPs) including MMP-9. The wide range of MMP-9 substrates, including ECM components and inflammatory cytokines, implicates MMP-9 in a variety of pathological and age-related processes. In particular, there is strong evidence that inflammatory cell-derived MMP-9 exacerbates cardiorenal aging. This review explores the potential therapeutic targets against CVD and CKD in the elderly, focusing on ECM and MMP roles.