Aging-related Changes in Cardiac Extracellular Matrix: Implications for Heart Failure in Older Patients

Abstract

The aging population with heart failure (HF) is increasing worldwide. Hypertension (HTN) and myocardial infarction (MI) are the two main comorbidities leading to HF in the elderly (age ≥ 65 years). Aging is progressive and results in cardiovascular changes that lead to an aging phenotype and negatively impact disease expression and response to therapy. Aging-related changes contribute to adverse cardiac remodeling and HF with preserved ejection fraction (HFpEF). HTN also leads to HFpEF whereas MI leads to HF with reduced EF (HFrEF). Aging and concomitant HTN or MI accelerates the march to HF. The cardiac extracellular matrix (ECM) is critical for maintaining cardiac shape/function. A key mechanism in the development and progression of HF due MI and HTN involves adverse cardiac ECM remodeling. Disruption of the ECM network and dysregulation of ECM homeostasis and metabolism result in adverse cardiac remodeling with shape deformation and dysfunction that lead to HF, disability and death. Agingrelated cardiac remodeling with superimposed progressive left ventricular remodeling leading to HFpEF or HFrEF in older patients is a persistent problem that has important therapeutic implications. Studies suggest that in the elderly, novel pathways can be targeted for optimizing therapy in HFrEF post-MI and HFpEF post-HTN. Therapeutic strategies that include targeting of adverse cardiac ECM remodeling could prevent/limit/reverse progression to HF in aging patients.