Alexander W. Clowes

Bio: Alexander W. Clowes is an academic researcher from University of Washington. The author has contributed to research in topics: Intimal hyperplasia & Vascular smooth muscle. The author has an hindex of 77, co-authored 225 publications receiving 20503 citations. Previous affiliations of Alexander W. Clowes include Brigham and Women's Hospital & University of Texas Health Science Center at Tyler.

Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty.

Abstract: Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for vascular smooth muscle cells (SMC) in vitro, but its activities in vivo remain largely undefined. We infused recombinant PDGF-BB (0.01-0.30 mg/kg per d i.v.) into rats subjected to carotid injury. PDGF-BB produced a small increase (two- to threefold) in medial SMC proliferation. More importantly, PDGF-BB greatly increased (20-fold) the intimal thickening and the migration of SMC from the media to the intima during the first 7 d after injury. These data provide support for the hypothesis that PDGF, and perhaps other platelet factors, might play an important role in the movement of mesenchymal cells into zones of injury undergoing repair.

Smooth muscle cell migration and matrix metalloproteinase expression after arterial injury in the rat.

Abstract: We have characterized matrix metalloproteinase expression in the rat carotid artery after two forms of arterial injury, balloon catheter denudation and nylon filament denudation. Gelatinolytic enzymes with molecular masses of 70 and 62 kD were produced constitutively in the rat carotid. Production of an 88-kD gelatinase was induced after balloon catheter injury, and proteinase production continued during the period of migration of smooth muscle cells from the media to the intima, from 6 hours to 6 days after balloon catheter injury. In addition, a marked increase in 62-kD gelatinolytic activity was observed between 4 and 14 days after arterial injury. Gelatinase activities (88 and 62 kD) were also increased after nylon filament denudation but were markedly less after this injury than after balloon catheter injury. These results suggested a correlation between gelatinase activity and smooth muscle cell migration after arterial injury. Administration of a metalloproteinase inhibitor after balloon catheter injury resulted in a 97% reduction in the number of smooth muscle cells migrating into the intima. Therefore, we hypothesize that gelatinase expression directly facilitates smooth muscle cell migration within the media and into the intima. These results suggest that gelatinases are involved in the vascular smooth muscle cell activation and neointimal formation that characterize arterial tissue remodeling after injury.

The pathogenesis of atherosclerosis: a perspective for the 1990s

Abstract: Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.

Isolation of putative progenitor endothelial cells for angiogenesis.

Abstract: Putative endothelial cell (EC) progenitors or angioblasts were isolated from human peripheral blood by magnetic bead selection on the basis of cell surface antigen expression In vitro, these cells differentiated into ECs In animal models of ischemia, heterologous, homologous, and autologous EC progenitors incorporated into sites of active angiogenesis These findings suggest that EC progenitors may be useful for augmenting collateral vessel growth to ischemic tissues (therapeutic angiogenesis) and for delivering anti- or pro-angiogenic agents, respectively, to sites of pathologic or utilitarian angiogenesis

Untangling the ErbB signalling network

Abstract: When epidermal growth factor and its relatives bind the ErbB family of receptors, they trigger a rich network of signalling pathways, culminating in responses ranging from cell division to death, motility to adhesion. The network is often dysregulated in cancer and lends credence to the mantra that molecular understanding yields clinical benefit: over 25,000 women with breast cancer have now been treated with trastuzumab (Herceptin), a recombinant antibody designed to block the receptor ErbB2. Likewise, small-molecule enzyme inhibitors and monoclonal antibodies to ErbB1 are in advanced phases of clinical testing. What can this pathway teach us about translating basic science into clinical use?

The Pathogenesis of Atherosclerosis — An Update

Abstract: CARDIOVASCULAR disease remains the chief cause of death in the United States and Western Europe, and atherosclerosis, the principal cause of myocardial and cerebral infarction, accounts for the majority of these deaths.1 This review, like its predecessor,2 will not attempt to cover all literature on atherosclerosis. In a previous review of the pathogenesis of atherosclerosis,2 Glomset and I discussed various hypotheses of atherogenesis2 3 4 5 6 7 and emphasized the importance of intimal smooth-muscle proliferation as the key event in the development of the advanced lesions of atherosclerosis. The response-to-injury hypothesis of atherogenesis2 3 4 5 6 proposes that "injury" to the endothelium is the initiating event in . . .