Cardiorenal
fibrosis is a biological process that increases with age and contributes to dysfunction of the heart and kidney. While numerous circulating and tissue
hormones,
cytokines and
enzymes have been identified in the development of cardiorenal
fibrosis, several reports have suggested that the anti-fibrotic
natriuretic peptide system (NPS), pro-fibrotic renin-angiotensin-aldosterone system (RAAS),
transforming growth factor-beta 1 (TGF-β1),
matrix metalloproteinases (
MMPs) and
tissue inhibitor of metalloproteinases (TIMPs) are fundamental regulators and mediators of this process. However, the simultaneous assessment of these components in the development of age-mediated cardiorenal fibrotic remodeling is not completely understood. Thus, we assessed cardiorenal structure and function, the circulating NPS and RAAS and the cardiorenal tissue gene expression of
collagen (Col) I, Col III, TGF-β1, MMP-9 and
TIMP-1 in 2 and 20 month old Fischer rats. Our studies determined that aging was characterized by an increase in cardiorenal
fibrosis that was accompanied with cardiorenal dysfunction. These alterations were associated with lower circulating atrial and C-type
natriuretic peptides and higher
angiotensin II and
aldosterone levels in the aged rats. Moreover, we observed a decrease in Col I and III and an increase in TIMP-
mRNA expressions in the aged heart and kidney, while TGF-β1 expression increased and MMP-9 decreased only in the aged kidney. We conclude that the age-mediated alterations in these fibrotic regulator and mediator profiles favors
collagen accumulation due to an imbalance between the NPS and RAAS as well as a decline in the degradative pathway, thus suggesting a therapeutic opportunity to target these components.