Philip M. Cummins

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Intercellular tight junctions (TJs) exhibit a complex molecular architecture involving the regulated cointeraction of cytoplasmic adaptor proteins (e.g., zonula occludens) and integral membrane linker proteins (e.g., occludin and claudins). They provide structural integrity to epithelial and endothelial tissues and create highly polarized barriers essential(More)
Notch signaling has been shown recently to regulate vascular cell fate in adult cells. By applying a uniform equibiaxial cyclic strain to vascular smooth muscle cells (SMCs), we investigated the role of strain in modulating Notch-mediated growth of SMCs in vitro. Rat SMCs cultured under conditions of defined equibiaxial cyclic strain (0% to 15% stretch; 60(More)
Vascular smooth muscle cell (SMC) fate decisions (cell growth, migration, and apoptosis) are fundamental features in the pathogenesis of vascular disease. We investigated the role of Notch 1 and 3 receptor signaling in controlling adult SMC fate in vitro by establishing that hairy enhancer of split (hes-1 and -5) and related hrt's (hrt-1, -2, and -3) are(More)
BACKGROUND AND OBJECTIVES Blood-brain barrier (BBB) dysfunction is an integral feature of neurological disorders and involves the action of multiple proinflammatory cytokines on the microvascular endothelial cells lining cerebral capillaries. There is still however, considerable ambiguity throughout the scientific literature regarding the mechanistic(More)
OBJECTIVE The vascular endothelium constitutes a highly effective fluid/solute barrier through the regulated apposition of intercellular tight junction complexes. Because endothelium-mediated functions and pathology are driven by hemodynamic forces (cyclic strain and shear stress), we hypothesized a dynamic regulatory link between endothelial tight junction(More)
OBJECTIVE To investigate the role of cyclic strain in controlling matrix metalloproteinase-2 (MMP-2) expression and activity in endothelial cells (ECs) in vitro. METHODS A Flexercell Tension Plus FX-4000T system was used to apply a physiological level of equibiaxial cyclic strain (0-10% strain, 60 cycles/min, 0-24 h, cardiac waveform) to bovine aortic(More)
Vascular smooth muscle cell (VSMC) phenotypic modulation is a key factor in vascular pathology. We have investigated the role of Notch receptor signaling in controlling human vascular smooth muscle cell (hVSMC) differentiation in vitro and established a role for cyclic strain-induced changes in Notch signaling in promoting this phenotypic response. The(More)
Pyroglutamyl peptidase can be classified as an omega peptidase which hydrolytically removes the amino terminal pyroglutamate (pGlu) residue from specific pyroglutamyl substrates. To date, three distinct forms of this enzyme have been identified in mammalian tissues. Type I is typically a cytosolic, cysteine peptidase displaying a broad pyroglutamyl(More)
Thrombomodulin (TM) is a 557-amino acid protein with a broad cell and tissue distribution consistent with its wide-ranging physiological roles. When expressed on the lumenal surface of vascular endothelial cells in both large vessels and capillaries, its primary function is to mediate endothelial thromboresistance. The complete integral membrane-bound(More)
Ion-exchange chromatography (IEC) allows for the separation of ionizable molecules on the basis of differences in charge properties. Its large sample-handling capacity, broad applicability (particularly to proteins and enzymes), moderate cost, powerful resolving ability, and ease of scale-up and automation have led to it becoming one of the most versatile(More)