David C Zawieja

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The concept of inflammation-induced lymphangiogenesis (ie, formation of new lymphatic vessels) has long been recognized, but the molecular mechanisms remained largely unknown. The 2 primary mediators of lymphangiogenesis are vascular endothelial growth factor receptor-3 (VEGFR-3) and Prox1. The key factors that regulate inflammation-induced transcription(More)
Here we show that endothelial cells (EC) require matrix type 1-metalloproteinase (MT1-MMP) for the formation of lumens and tube networks in 3-dimensional (3D) collagen matrices. A fundamental consequence of EC lumen formation is the generation of vascular guidance tunnels within collagen matrices through an MT1-MMP-dependent proteolytic process. Vascular(More)
Lymphatics are necessary for the generation and regulation of lymph flow. Lymphatics use phasic contractions and extrinsic compressions to generate flow; tonic contractions alter resistance. Lymphatic muscle exhibits important differences from typical vascular smooth muscle. In this study, the thoracic duct exhibited significant functional differences from(More)
OBJECTIVE To evaluate lymphatic contractile activity in different regions of the lymphatic system in a single animal model (the rat thoracic duct, mesenteric, cervical, and femoral lymphatics) in response to changes in lymph pressure and flow. METHODS The systolic and diastolic diameters of isolated, cannulated, and pressurized lymphatic vessels were(More)
Aging is associated with an increased incidence and severity of acute renal failure. However, the molecular mechanism underlying the increased susceptibility to injury remains undefined. These experiments were designed to investigate the influence of age on the response of the kidney to ischemic injury and to identify candidate genes that may mediate this(More)
The effect of bradykinin (BK) on cytosolic calcium in coronary venular endothelial cells (CVEC) was studied using the intracellular calcium indicator indo 1. At normal extracellular calcium levels, CVEC responded to BK at concentrations as low as 0.1 pM; maximum cytosolic calcium spikes occurred at 10 nM. In calcium-free medium, poststimulation cytosolic(More)
A normal heart increases its contractile force with increasing heart rate. Although calcium handling and myofibrillar proteins have been implicated in maintaining this positive force-frequency relationship (FFR), the exact mechanisms by which it occurs have not been addressed. In this study, we have developed an analytical method to define the calcium-force(More)
Pre-eclampsia (preE), a pregnancy disorder with the de novo onset of hypertension and proteinuria after 20 weeks of gestation, has multiple triggers that initiate pathophysiologic mechanisms. This review addresses translational aspects of preE by synthesizing information on preE pathogenesis, describing diagnostic biomarkers that predict disease, and(More)
The contractile properties of the mesenteric collecting lymphatics of the rat were analyzed under control conditions and during periods of enhanced lymph formation using in vivo microscopic techniques. Pressure and diameter were simultaneously monitored in microscopic collecting lymphatics, and lymphatic pump function was analyzed in accordance with basic(More)
OBJECTIVE To measure lymphocyte velocity, lymphatic contraction, and shear stress in phasically contracting lymphatics in situ. METHODS A high-speed video system was used to capture multiple contraction cycles in rat mesenteric lymphatic preparations. The images were analyzed to determine fluid velocity, volume flow rate, wall shear stress, and retrograde(More)