Elastin microfibril interface-located protein 1, transforming growth factor beta, and implications on cardiovascular complications

Abstract

Elastin microfibril interface-located protein 1 (EMILIN1), a glycoprotein, is associated with elastin in the extracellular matrix (ECM) of arteries, lymph vasculature, and other tissues. EMILIN1 particularly has a niche role in elastin fiber biogenesis (elastogenesis) by aiding with the fusion of elastin fibers, rendering them more ordered. In addition to elastogenesis, EMILIN1 has been shown to have roles in maintenance of vascular cell morphology, smooth muscle cell adhesion to elastic fibers, and transforming growth factor (TGFβ) regulation, by inhibiting TGFβ activation via blocking the proteolytic production of the latency-associated peptide/active TGFβ complex. The increased TGFβ signaling induced during EMILIN1 deficiency alters TGFβ activity, resulting in vascular smooth muscle cell growth and vascular remodeling. The increasing systemic blood pressure associated with TGFβ signaling may be closely linked to the activity of other mediators that affect cardiovascular homeostasis, such as angiotensin II. The increase in prevalence of hypertension and other cardiovascular diseases in other disease states likely involve a complex activation of TGFβ signaling and ECM dysfunction. Thus, the interaction of TGFβ and ECM components appears to be integrative involving both structural alterations to vessels through EMILIN1 and changes in TGFβ signaling processes. This review summarizes the current knowledge on the EMILIN1-TGFβ relationship; the specific roles of EMILIN1 and TGFβ in blood pressure regulation, their synergistic interaction, and in particular the role of TGFβ (in conjunction with ECM proteins) in other disease states altering cardiovascular homeostasis.