Matrix metalloproteinase‐9 deletion attenuates age‐related periostin induction and diastolic dysfunction in mice

Abstract

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).