The aging heart, myocardial fibrosis, and its relationship to circulating C-type natriuretic peptide

S. Jeson Sangaralingham, Brenda K. Huntley, Fernando L. Martin, Paul M. McKie, Diego Bellavia, Tomoko Ichiki, Gerald E. Harders, Horng H. Chen, John C. Burnett

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Myocardial aging is characterized by left ventricular (LV) fibrosis leading to diastolic and systolic dysfunction. Studies have established the potent antifibrotic and antiproliferative properties of C-type natriuretic peptide (CNP); however, the relationship between circulating CNP, LV fibrosis, and associated changes in LV function with natural aging are undefined. Accordingly, we characterized the relationship of plasma CNP with LV fibrosis and function in 2-, 11-, and 20-month-old male Fischer rats. Further in vitro, we established the antiproliferative actions of CNP and the participation of the clearance receptor using adult human cardiac fibroblasts. Here we establish for the first time that a progressive decline in circulating CNP characterizes natural aging and is strongly associated with a reciprocal increase in LV fibrosis that precedes impairment of diastolic and systolic function. Additionally, we demonstrate in cultured adult human cardiac fibroblasts that the direct antiproliferative actions of high-dose CNP may involve a non-cGMP pathway via the clearance receptor. Together, these studies provide new insights into myocardial aging and the relationship to the antifibrotic and antiproliferative peptide CNP.

Original languageEnglish (US)
Pages (from-to)201-207
Number of pages7
JournalHypertension
Volume57
Issue number2
DOIs
StatePublished - Feb 1 2011

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Keywords

  • C-type natriuretic peptide
  • aging
  • fibrosis
  • heart
  • natriuretic peptides

ASJC Scopus subject areas

  • Internal Medicine

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