Perturbation of the smooth muscle cells (SMC) in the vascular wall, resulting in proliferation and migration, is the basic cause of fibrous/fibrofatty accumulation and intimal thickening, i.e., atherosclerosis, the major cause of vascular disease. In order to understand the biology of the SMC and the physiological basis for the sudden changes in the phenotype of the media] SMCs, we propose to investigate the molecular biology and kinetics of single SMCs from rabbit vascular tissue under normal and experimentally induced pathological conditions. This information will help us understand the kinetic properties of individual SMCs and the contractile protein myosin isoform composition in physiological and pathological (atherosclerosis) conditions. As a prelude to understand the cellular biology of medial SMCs that form the intimal thickening in atherosclerosis, we propose to determine: a) the distribution of the different types of SMCs along the arterial tree in the context of their mechanical properties, b) possible correlations between the kinetics of SMC mechanics and the diversity in the molecular composition of the contractile machinery, and c) changes in these properties under experimentally induced pathological conditions. Specifically, we propose to study the physical and mechanical properties (i.e., cell size, unloaded shortening velocity, extent of shortening, force production) of the same arterial smooth muscle cell.
The specific aims of this investigation are to determine: 1) the diversity of SMC types in terms of myosin isoform composition in different regions of the arterial wall, 2) correlation of myosin isoform composition with the variations in cell mechanics, 3) if the myosin heavy chain (MHC) and myosin light chain (MLC) isoforms are coordinately regulated, and 4) if any of the specific medial wall cell types are selectively more prone to migration and proliferation (resulting in intimal thickening) with perturbation of the endothelial wall. The results obtained in these studies will throw light on the cellular origin of the atheroma.
|Eddinger, Thomas J (2014) Smooth muscle-protein translocation and tissue function. Anat Rec (Hoboken) 297:1734-46|
|Huang, Qian; Babu, Gopal J; Periasamy, Muthu et al. (2013) SMB myosin heavy chain knockout enhances tonic contraction and reduces the rate of force generation in ileum and stomach antrum. Am J Physiol Cell Physiol 304:C194-206|
|Eddinger, Thomas J (2009) Unique contractile and structural protein expression in dog ileal inner circular smooth muscle. J Smooth Muscle Res 45:217-30|
|Govindaraju, Sandya R; Bain, James Lw; Eddinger, Thomas J et al. (2008) Vibration causes acute vascular injury in a two-step process: vasoconstriction and vacuole disruption. Anat Rec (Hoboken) 291:999-1006|
|Eddinger, Thomas J; Meer, Daniel P; Miner, Amy S et al. (2007) Potent inhibition of arterial smooth muscle tonic contractions by the selective myosin II inhibitor, blebbistatin. J Pharmacol Exp Ther 320:865-70|
|Eddinger, Thomas J; Schiebout, Jessen D; Swartz, Darl R (2007) Adherens junction-associated protein distribution differs in smooth muscle tissue and acutely isolated cells. Am J Physiol Gastrointest Liver Physiol 292:G684-97|
|Eddinger, Thomas J; Meer, Daniel P (2007) Myosin II isoforms in smooth muscle: heterogeneity and function. Am J Physiol Cell Physiol 293:C493-508|
|Han, Shaojie; Speich, John E; Eddinger, Thomas J et al. (2006) Evidence for absence of latch-bridge formation in muscular saphenous arteries. Am J Physiol Heart Circ Physiol 291:H138-46|
|Call, Christopher; Han, Shaojie; Speich, John E et al. (2006) Resistance to pressure-induced dilatation in femoral but not saphenous artery: physiological role of latch? Am J Physiol Heart Circ Physiol 291:H1513-20|
|Eddinger, Thomas J; Schiebout, Jessen D; Swartz, Darl R (2005) Smooth muscle adherens junctions associated proteins are stable at the cell periphery during relaxation and activation. Am J Physiol Cell Physiol 289:C1379-87|
Showing the most recent 10 out of 16 publications