Differential responses to thrombospondin-1 and PDGF-BB in smooth muscle cells from atherosclerotic coronary arteries and internal thoracic arteries.

Atherosclerosis is rare in internal thoracic arteries (ITA) even in patients with severe atherosclerotic coronary artery (ACA) disease. To explore cellular differences, ITA SMC from 3 distinct donors and ACA SMC from 3 distinct donors were grown to sub-confluence and growth arrested for 48 h. Proliferation and thrombospondin-1 (TSP1) production were determined using standard techniques.

Expression of Cyr61 in ApoE mice with chronic unilateral renal artery ligation.

Cyr61 is a member of the CCN family of proteins that is expressed in atherosclerotic lesions and regulated by angiotensin II. It is unknown whether renal artery stenosis (RAS) increases Cyr61 expression. Male ApoE mice were randomized to surgically induced RAS, RAS + treatment with either irbesartan, aliskiren or amlodipine or sham-surgery.

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE-/- Mice With Unilateral Renal Artery Stenosis.

Background: Chronic unilateral renal artery stenosis (RAS) causes accelerated atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice, but effects of restoration of renal blood flow on aortic atherosclerosis are unknown.

Methods And Results: Male ApoE(-/-) mice underwent sham surgery (n=16) or had partial ligation of the right renal artery (n=41) with the ligature being removed 4 days later (D4LR; n=6), 8 days later (D8LR; n=11), or left in place for 90 days (chronic RAS; n=24). Ligature removal at 4 or 8 days resulted in improved renal blood flow, decreased plasma angiotensin II levels, a return of systolic blood pressure to baseline, and increased plasma levels of neutrophil gelatinase associated lipocalin.

Perivascular delivery of blebbistatin reduces neointimal hyperplasia after carotid injury in the mouse.

Proliferation and migration of smooth muscle cells (SMC) require myosin II activity; thus, we examined whether blebbistatin, a cell-permeable selective inhibitor of myosin II ATP activity, would impair neointimal hyperplasia after vascular injury. Delivery of blebbistatin via a perivascular polymer cuff reduced neointimal formation by 73% and luminal obstruction by 75% after carotid denudation injury in C57BL/6 mice. Blebbistatin treatment was also associated with a reduction in cell density within the neointima; total number of cells (76 ± 7 to 27 ± 3 cells/high-powered field) and actin-positive cells (64 ± 4 to 24 ± 2 cells/high-powered field) in the neointima were reduced in blebbistatin-treated mice compared with vehicle-treated mice.

Activation of protease-activated receptors 3 and 4 accelerates tissue factor-induced thrombin generation on the surface of vascular smooth muscle cells.

Objective: To determine factors regulating human aortic smooth muscle cells (HASMC) supported tissue factor-induced thrombin generation.

Methods And Results: The addition of nonlipidated tissue factor and Ca(2+) to HASMCs maintained in reptilase-treated platelet-poor plasma resulted in the robust formation of thrombin after a lag phase of approximately 6 minutes. Pretreatment with low concentrations of α-thrombin before the addition of tissue factor and Ca(2+) accelerated the rate of thrombin generation (time to reach half of peak thrombin was reduced by [mean ± SD] 42.

Eptifibatide and abciximab inhibit insulin-induced focal adhesion formation and proliferative responses in human aortic smooth muscle cells.

Background: The use of abciximab (c7E3 Fab) or eptifibatide improves clinical outcomes in diabetics undergoing percutaneous coronary intervention. These beta3 integrin inhibitors antagonize fibrinogen binding to alphaIIbbeta3 integrins on platelets and ligand binding to alphavbeta3 integrins on vascular cells. alphavbeta3 integrins influence responses to insulin in various cell types but effects in human aortic smooth muscle cells (HASMC) are unknown.

beta(3)-Integrin cytoplasmic binding proteins.

Integrins are cell-surface adhesion receptors that play an important role in mediating numerous physiological processes,including inflammation, migration, adhesion, and proliferation. Integrin regulation by events within the cell has been termed "inside-out " signaling; this is a capacity that is unique to integrin receptors. As is typical of other cell-surface receptors, integrins can also transduce signals from outside the cell into the cytoplasm on binding extracellular ligands ("outside-in signaling ").