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Research Article

EJMCM. 2014; 2(1): 16-19


Small molecule PAI-1 functional inhibitor attenuates vascular smooth muscle cell migration and survival: Implications for the therapy of vascular disease

Tessa M. Simone, Paul J. Higgins.

Abstract
Focal points

Bedside

Targeted pharmacologic disruption of PAI-1 function with small molecule inhibitors may have general applicability for the treatment of fibroproliferative disorders, in general, and vascular disease, in particular. The development orally compatible drugs would likely simplify delivery and patient compliance.


Benchside

It is apparent that PAI-1 is a multi-functional SERPIN, affecting such diverse physiological and pathophysiological processes as smooth muscle cell growth, migration, survival and pericellular proteolysis activity. Clearly, PAI-1 functional blockade has widespread clinical implications that are not restricted to one aspect of the tissue response to injury.


Industry

The original small molecule panel of PAI-1 inhibitors derived from a collaboration between basic scientists and, largely, cardiovascular disease-oriented medical chemists as well as pharmaceutical investigators. This collegial relationship is expected to expand as it is evident that PAI-1 inhibition has generally utility in the treatment of cardiovascular diseases, tissue fibrosis (in particular, the renal and pulmonary systems) and cancer.

Key words: Vascular diseasePAI-1SERPINPericellular proteolysisTiplaxtininVascular smooth muscle cellsMigrationApoptosis



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