Hevin Promotes Aging-Related Cardiac Dysfunction via Facilitating Cardiac Inflammation in Male Mice

Area of Science:

• Cardiovascular Biology
• Immunology
• Aging Research

Background:

• Aging is associated with increased systemic inflammation, involving macrophages and contributing to tissue damage and disease.
• Hevin (SPARCL1) is implicated in inflammatory responses and macrophage polarization, suggesting a role in age-related conditions.
• Cardiac aging is a significant health concern, characterized by functional decline and increased susceptibility to disease.

Purpose of the Study:

• To investigate the role of Hevin in the aging process of the heart.
• To elucidate the molecular mechanisms by which Hevin influences cardiac aging and function.
• To identify Hevin as a potential therapeutic target for age-related cardiac dysfunction.

Main Methods:

• Utilized young and aging C57 BL/6 male mice, administering Hevin or using adeno-associated virus serotype 9 (AAV9) vectors for Hevin knockdown.
• Employed RNA sequencing (RNA-seq) to analyze molecular changes in aging hearts.
• Investigated Hevin's role in macrophage polarization using RAW264.7 cell lines.

Main Results:

• Aging mice exhibited higher serum Hevin levels and increased cardiac Hevin expression, correlating with impaired cardiac function.
• Hevin administration exacerbated aging-related cardiac remodeling and dysfunction, while Hevin knockout ameliorated these effects.
• Hevin induced CCL5 activation in aging hearts; blocking CCL5 reversed Hevin's detrimental effects on cardiac aging in vivo.

Conclusions:

• Hevin promotes cardiac aging and dysfunction by stimulating cardiac macrophages via TLR4, leading to CCL5 release and increased inflammation.
• Hevin serum levels and cardiac expression are inversely correlated with cardiac function during aging.
• Targeting Hevin presents a promising strategy for predicting and treating cardiac aging and associated inflammatory conditions.