Cellular Components of the Coronary Vasculature Exhibit Differential Sensitivity to Low Temperature Insult

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Abstract
In the treatment of atherosclerosis, therapeutic angioplasty is commonly used to restore normal blood flow in stenosed arteries. This procedure, however, is associated with vascular endothelial cell erosion (denudation) of the intimal lining and subsequent acute arterial closure through restenosis, which involves the encroachment of vascular smooth muscle cells from the medial layer into the lumen. In the vasculature of the heart, coronary artery endothelial cells (CAECs) and coronary artery smooth muscle cells (CASMCs) are major players in the pathogenesis of atherosclerosis in the vasculature of the heart. Interactions between these cell types and the innate immune response are paramount to atherosclerosis and post-intervention complications. The objective of this study was to investigate/optimize the efficacy of cryotherapy (the endovascular application of low temperature) as an adjunctive therapeutic intervention in association with angioplasty to combat restenosis. We report on an in vitro model for the assessment of cellular response to transient low temperature insults on human CAECs and CASMCs. Fluorescent probes were employed to assess various parameters of overall cell culture viability following exposure to temperatures ranging from 37°C to -60°C. Specific fluorescent indicators measured relative metabolic activity/respiration (alamarBlue™; Accumed International, Westlake, OH), membrane integrity (calcein-acetoxymethyl ester), and cell number (SYTO® 24; Molecular Probes, Eugene, OR). The results demonstrated that CAECs are not only more resistant to the cold, but that they also yield an increased proliferative ability over cold-exposed CASMCs. Our data demonstrate that human CAECs and CASMCs respond differentially to thermal stress and may provide insight into the optimization of cryotherapy to prevent restenosis in vivo.