Extracellular Matrix Remodeling in Vascular Development and Disease

Abstract

Blood vessels constantly subjected to mechanical stress have well-developed elastic fiber-rich frameworks, which contribute to the elasticity and distensibility of the vascular wall. Destruction of the fibrous structure due to genetic predisposition as well as acquired disorders such as Kawasaki disease often induces irreversible dilation of blood vessels, e.g., aneurysm formation. In addition to their structural role, extracellular matrix molecules also provide important biological signaling, which influences various cellular functions. Among them, increased attention has been focused on matricellular proteins, a group of nonstructural extracellular matrix (ECM) proteins highly upregulated in active tissue remodeling, serving as biological mediators by interacting directly with cells or regulating the activities of growth factors, cytokines, proteases, and other ECM molecules. Tenascin-C (TNC) is a typical matricellular protein expressed during embryonic development and tissue repair/regeneration in a spatiotemporally restricted manner. Various growth factors, pro-inflammatory cytokines, and mechanical stress upregulate its expression. TNC controls cell adhesion, migration, differentiation, and synthesis of ECM molecules. Our recent results suggest that TNC may not only play a significant role in the recruitment of smooth muscle/ mural cells during vascular development, but also regulate the inflammatory response during pathological remodeling. TNC may be a key molecule during vascular development, adaptation, and pathological tissue remodeling.

The Role of Toll-Like Receptor Signaling in the Progression of Heart Failure

“…ROS can modify membrane components and can cause the release of factors that interact with and activate TLR4 to induce cardiomyocyte apoptosis and HF [ 10 , 65 ]. Tenascins represent a family of four multimeric extracellular matrix glycoproteins [ 66 ]. Serum level of tenascin C (TNC) correlates with the severity of HF [ 67 ].…”

Regulation of Myocardial Extracellular Matrix Dynamic Changes in Myocardial Infarction and Postinfarct Remodeling

“…Tenascin-C also induces fibroblast migration into the remodeling area and myofibroblast transformation promoting myocardial fibrosis and diastolic dysfunction [ 103 ]. In addition, tenascin-C possesses elastic properties that help to prevent mechanical overload of the border zone [ 104 ]. Some studies show that tenascin-C is cleaved by MMP-2 that unfolds its cryptic adhesive site, and conversely, tenascin-C can induce the expression of MMPs that potentiates structural matrix destruction [ 105 ].…”

The Extracellular Matrix Protein ABI3BP in Cardiovascular Health and Disease

“…Thus, ABI3BP may help maintain the non-proliferative state of the normal myocardium. Further, cell-extracellular matrix interactions are key in the heart and vasculature to organize the organ structure; provide biological, biochemical, and biophysical signals between the intracellular and extracellular environments; and provide mechanical strength against blood flow ( 31 – 35 ). ABI3BP may be an important component of the cell-extracellular matrix interactome in the cardiovascular system.…”

“…ABI3BP may be an important component of the cell-extracellular matrix interactome in the cardiovascular system. Moreover, pathological extracellular matrix remodeling is a key feature of many cardiovascular diseases ( 35 , 36 ). This pathological remodeling may affect or be affected by ABI3BP.…”

“…Furthermore, our study showed that ABI3BP levels were significantly reduced in failing human hearts with dilated cardiomyopathy ( 37 ). Pathological remodeling of the extracellular matrix of the heart and vasculature during the progression of cardiovascular disease plays an important role in disease pathology ( 35 , 36 ). Thus, alteration of ABI3BP expression in the extracellular matrix during cardiovascular disease can be a cause and/or consequence of pathological remodeling.…”