title: Aging and the cardiac collagen matrix: Novel mediators of fibrotic remodelling.
abstract: Cardiovascular disease is a leading cause of death worldwide and there is a pressing need for new therapeutic strategies to treat such conditions. The risk of developing cardiovascular disease increases dramatically with age, yet the majority of experimental research is executed using young animals. The cardiac extracellular matrix (ECM), consisting predominantly of fibrillar collagen, preserves myocardial integrity, provides a means of force transmission and supports myocyte geometry. Disruptions to the finely balanced control of collagen synthesis, post-synthetic deposition, post-translational modification and degradation may have detrimental effects on myocardial functionality. It is now well established that the aged heart is characterized by fibrotic remodelling, but the mechanisms responsible for this are incompletely understood. Furthermore, studies using aged animal models suggest that interstitial remodelling with disease may be age-dependent. Thus with the identification of new therapeutic strategies targeting fibrotic remodelling, it may be necessary to consider age-dependent mechanisms. In this review, we discuss remodelling of the cardiac collagen matrix as a function of age, whilst highlighting potential novel mediators of age-dependent fibrotic pathways.
authors.affiliation: Institute of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, 3.06 Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, United Kingdom. Electronic address: margaux.horn@manchester.ac.uk.
authors.forename: Margaux A
authors.initials: MA
authors.lastname: Horn
authors.affiliation: Institute of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, 3.06 Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, United Kingdom.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Trafford
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D011499:Protein Processing, Post-Translational; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D018754:Ventricular Dysfunction / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases
keywords: Aging; Collagen; Extracellular matrix; Fibrosis; Heart failure