The role of inflammatory and fibrogenic pathways in heart failure associated with aging.
Heart failure is strongly associated with aging. Elderly patients with heart failure often have preserved systolic function exhibiting left ventricular hypertrophy accompanied by a decline in diastolic function. Experimental studies have demonstrated that age-related cardiac fibrosis plays an important role in the pathogenesis of diastolic heart failure in senescent hearts. Reactive oxygen species and angiotensin II are critically involved in fibrotic remodeling of the aging ventricle; their fibrogenic actions may be mediated, at least in part, through transforming growth factor (TGF)-beta. The increased prevalence of heart failure in the elderly is also due to impaired responses of the senescent heart to cardiac injury. Aging is associated with suppressed inflammation, delayed phagocytosis of dead cardiomyocytes, and markedly diminished collagen deposition following myocardial infarction, due to a blunted response of fibroblasts to fibrogenic growth factors. Thus, in addition to a baseline activation of fibrogenic pathways, senescent hearts exhibit an impaired reparative reserve due to decreased responses of mesenchymal cells to stimulatory signals. Impaired scar formation in senescent hearts is associated with accentuated dilative remodeling and worse systolic dysfunction. Understanding the pathogenesis of interstitial fibrosis in the aging heart and dissecting the mechanisms responsible for age-associated healing defects following cardiac injury are critical in order to design new strategies for prevention of adverse remodeling and heart failure in elderly patients.
Chen
Wei
W
Section of Cardiovascular Sciences, Baylor College of Medicine, One Baylor Plaza BCM620, Houston, TX 77030, USA.
Frangogiannis
Nikolaos G
NG
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000804:Angiotensin II; D005347:Fibroblasts / Q000473:pathology*; D005355:Fibrosis / Q000503:physiopathology; D054144:Heart Failure, Diastolic / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D032342:Muscle Cells; D010586:Phagocytes; D017382:Reactive Oxygen Species; D012307:Risk Factors; D016212:Transforming Growth Factor beta; D014481:United States / Q000453:epidemiology; D020257:Ventricular Remodeling
D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D000804:Angiotensin II