Aortic Tropoelastin Degradation by MFG-E8 Directed p38 mediated signaling

Authors

• SH Kim
• RE Monticone
• Z Zhang
• M Wang
• EG Lakatta

Abstract

Arterial stiffness, a risk factor for cardiovascular disease that is independent of blood pressure, increases as we age. In addition, there is an increase in aortic wall collagen, and increased arterial stiffness which occurs in the context of elastin fiber fragmentation and elastin structural disorganization in which p38 activation has been implicated. Milk fat globule-EGF factor 8(MFG-E8), a.k.a. Lactadherin, a proinflammatory molecule secreted from VSMCs, also increases in the arterial wall with age and colocalizes with the elastin laminae in stiffened arterial walls. Whether or how MFG-E8 signaling affects age-associated elastin remodeling, however, is unknown. We tested the hypothesis that MFG-E8 signaling is central to the molecular mechanisms of elastin remodeling with age in the arterial wall. Methods: We studied both thoracic aortic tissue and cultured VSMCs from young (8mo) and old (30mo) F344XBN male rats. Immunoblotting was performed with antibodies against Tropoelastin, MFG-E8, p-p38, and MMP-2. Recombinant human MFG-E8 protein was used for MFG-E8 overexpression and transfected VSMCs with lipofectamine silencing. Statistical Analyses: Student’s t-tests and one-way ANOVA. Results: Aging reduces Tropoelastin expression by 76.7% in aortic tissue and 65.9% in VSMC (both p

Scientific Focus Area: Cell Biology

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