Continuous pressure overload induces myocardial hypertrophy as an adaptive response. Cardiac fibrosis often follows hypertrophy to prevent myocytes from overextension. However, massive fibrosis makes cardiac function impaired, which is a maladaptive response. Although a considerable number of studies have demonstrated a series of transcriptional pathways, it still remains equivocal which molecule (s) plays an important role in initiation of cardiac fibrosis. Therefore, it is important to identify a molecular inducer of fibrosis as a therapeutic target for heart failure. A rat model of cardiac hypertrophy and fibrosis were generated by pulmonary artery banding (PAB).
　Four to six weeks after operation, histological analyses with Masson Trichrome stain on short axis section of right ventricular papillary muscles identified that they could be clearly divided into the interstitial fibrosis group (Fibrosis; 17.1±1.5% of fibrosis area) and the non-fibrotic, but hypertrophic group (Hypertrophy; 3.0±0.3%) , in comparison with the sham-operated control (Sham; 2.5±0.2%). We comprehensively analyzed the mRNA expression of 29215 known rat genes in the right ventricle by using GeneChip® Rat Gene 1.0 ST Array (Affymetrix®) to compare a gene expression profile among Sham, Hypertrophy, and Fibrosis (n=3 each) . We found that the expression levels of some genes that have not been recognized as a fibrosis-related molecule were significantly higher in Fibrosis than those in Sham and Hypertrophy. Among them, we selected FGF23 and Ncam1, and confirmed expression levels of these genes by RT-PCR (n=6 each). Using OLETF rats under exercise, we found that adult exercise group rapidly gained body weight when they stopped exercise, and showed significantly higher expression levels of FGF23, Ncam1 and TGF-beta than those in OLET-F young exercise and OLET-F non-exercise group. These data suggest that 1) FGF23 and NCAM1 can be used for cardiac fibrosis-related biomarker and 2) stopping exercise followed by rapid weight gain would be one of the risk factors for cardiac fibrosis.

DESCENTE SPORTS SCIENCE Vol.35/THE DESCENTE AND ISHIMOTO MEMORIAL FOUNDATION FOR THE PROMOTION SPORTS SCIENCE