Role of β1 and β3 Integrins in Human Smooth Muscle Cell Adhesion to and Contraction of Fibrin Clots In Vitro

Abstract

Abstract-The degree of lumen narrowing in advanced lesions correlates poorly with the amount of intimal mass accumulated in the atherosclerotic plaque. As an alternate mechanism of stenosis, we propose that human smooth muscle cells bind to fibrin deposited in the matrix and exert contractile forces to cause a narrowing of the lumen. In the present study we demonstrated in vitro that human newborn aortic smooth muscle cell lines can contract and adhere to fibrin clots composed of either fibronectin-depleted plasma ("plasma") or recombinant fibrin. By using neutralizing antibodies and RGD peptides, we showed that members of the integrin family mediated the interaction between human newborn smooth muscle cells and fibrin. Neutralizing antibodies against the integrin ␣v␤3 (c7E3 Fab and LM609) did not inhibit either plasma clot contraction or recombinant fibrin clot contraction by human newborn smooth muscle cells. In contrast, antibodies against ␣5, ␤1, and ␣5␤1 inhibited contraction of clots composed of either plasma or recombinant fibrin. Anti-␣v␤3, anti-␣v, anti-␣5, anti-␤1, and anti-␣5␤1 antibodies inhibited human newborn smooth muscle cell adhesion to plasma clots; however, only anti-␣5, anti-␤1, and anti-␣5␤1 antibodies significantly inhibited adhesion to recombinant fibrin. While the linear RGD peptides had no effect, the cyclic peptide penRGD inhibited adhesion to plasma clots and recombinant fibrin. However, it did not block contraction of recombinant fibrin clots. These results suggest that during the interaction of human newborn smooth muscle cell lines with fibrin, ␣5␤1 plays a significant role. This interaction is of potential interest as a target for efforts to block vascular contraction. (Circ Res. 1998;83:241-251.)

Molecular characterization and expression analysis of the gene coding for the porcine β3 integrin subunit (CD61)

“…Thus, the expression of the CD61 protein in porcine vascular and non-vascular smooth muscle could be due to the presence of α v β 3 as it was reported in previous studies in human (Yee et al, 1998). Similarly, the positive reaction found in myeloid cells would be expected on the basis of the presence of α IIb β 3 in human platelets and megakaryocytes (Heijnen et al, 1998) and α v β 3 in monocytes, macrophages and granulocytes from different species (Singh et al, 2001).…”

Selective regulation of integrin–cytoskeleton interactions by the tyrosine kinase Src

“…Reinforcement of integrin-cytoskeleton linkages is inversely related to cell motility and may account for the failure of osteoclasts to resorb bone in Src-deficient mice. However, the ability of cells to generate sustained forces through adhesion sites may be essential to other cell functions, including wound closure and the maintenance of tissue architecture 29 . ᮀ…”

Ziziphus nummularia Inhibits Inflammation‐Induced Atherogenic Phenotype of Human Aortic Smooth Muscle Cells

“…Importantly, the upregulation of α 5 β 1 integrin in the neointimal lumen is thought to critically augment VSMCs adhesion to fibronectin during inflammation [36]. With a suggested role in fibrin adhesion and fibrin clot formation [37], α 5 β 1 could contribute to luminal narrowing of the vessel because of the abundancy of both fibrin and fibronectin in the atherosclerotic lesion [38]. Our results showed that the treatment of HASMCs with ZNE significantly inhibited their fibronectin adhesive capacity.…”