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Matrix metalloproteinase‐9 deletion attenuates age‐related periostin induction and diastolic dysfunction in mice
Author(s) -
Chiao Ying Ann,
Jin YuFang,
Shamhart Patricia,
Zamilpa Rogelio,
Dai Qiuxia,
Ramirez Trevi,
Zhang Jianhua,
Lindsey Merry
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1096.4
Subject(s) - periostin , matrix metalloproteinase , medicine , diastole , matrix metalloproteinase 9 , matrix (chemical analysis) , endocrinology , cardiology , biology , chemistry , microbiology and biotechnology , extracellular matrix , blood pressure , chromatography
Diastolic dysfunction is a characteristic of cardiac aging, and altered extracellular matrix structure has been shown to regulate diastolic function. Matrix metalloproteinase‐9 (MMP‐9) levels increase with age in the left ventricle (LV), but a causal link between MMP‐9 and age‐related diastolic dysfunction has not been established. To investigate the role of MMP‐9 on diastolic function, Doppler echocardiography was performed on young and senescent WT and MMP‐9 null mice (n=5–7 per group). The peak early to late diastolic filling velocity ratio (E/A ratio) decreased from 1.5±0.2 in young WT to 1.1±0.1 in senescent WT mice (p<0.05). Strikingly, the E/A ratio of senescent MMP‐9 null mice was similar to the young null value (1.3±0.1 vs 1.4±0.2, p=ns), indicating that the decline in diastolic function in senescent WT was attenuated by MMP‐9 deletion. By real‐time PCR, periostin mRNA levels increased in senescent WT but not MMP‐9 null LV compared to young controls, and senescent WT LV expressed higher levels of periostin than senescent MMP‐9 null LV (all p<0.05). Periostin regulates collagen fibrillogenesis and fibroblast‐myocyte interactions, two processes that can modulate myocardial stiffness. In conclusion, MMP‐9 deletion attenuates the age‐related decline in diastolic function in mice, potentially by suppressing periostin induction. UTHSCSA TST (YAC), NIH 1SC2 HL101430 (YJ), and VA Merit Award (MLL).