Cardiorenal fibrosis and dysfunction in aging: Imbalance in mediators and regulators of collagen

S Jeson Sangaralingham, Bing H. Wang, Li Huang, Sirinart Kumfu, Tomoko Ichiki, Henry Krum, John C Jr. Burnett

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)108-114
Number of pages7
JournalPeptides
Volume76
DOIs
StatePublished - Feb 1 2016

Fingerprint

Aldosterone
Natriuretic Peptides
Angiotensins
Fibrosis
Collagen
Renin-Angiotensin System
Aging of materials
Renin
Transforming Growth Factor beta
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 9
Kidney
Rats
C-Type Natriuretic Peptide
Tissue
Biological Phenomena
Matrix Metalloproteinase 1
Tissue Inhibitor of Metalloproteinase-1
Inbred F344 Rats

Keywords

  • Cardiorenal
  • Fibrosis
  • Gene expression
  • Natriuretic peptides
  • Renin-angiotensin-aldosterone system

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

Cardiorenal fibrosis and dysfunction in aging : Imbalance in mediators and regulators of collagen. / Sangaralingham, S Jeson; Wang, Bing H.; Huang, Li; Kumfu, Sirinart; Ichiki, Tomoko; Krum, Henry; Burnett, John C Jr.

In: Peptides, Vol. 76, 01.02.2016, p. 108-114.

Research output: Contribution to journalArticle

Sangaralingham, S Jeson ; Wang, Bing H. ; Huang, Li ; Kumfu, Sirinart ; Ichiki, Tomoko ; Krum, Henry ; Burnett, John C Jr. / Cardiorenal fibrosis and dysfunction in aging : Imbalance in mediators and regulators of collagen. In: Peptides. 2016 ; Vol. 76. pp. 108-114.
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AB - 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.

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