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BACKGROUND Alveolar hypoxia acutely elicits pulmonary vasoconstriction (HPV). Chronic hypoxia (CH), despite attenuating HPV, causes pulmonary hypertension (CH-PHT). HPV results, in part, from inhibition of O2-sensitive, voltage-gated potassium channels (Kv) in pulmonary artery smooth muscle cells (PASMCs). CH decreases Kv channel current/expression and(More)
BACKGROUND Chronic hypoxic pulmonary hypertension (CH-PHT) is associated with suppressed expression and function of voltage-gated K(+) channels (Kv) in pulmonary artery (PA) smooth muscle cells (SMCs) and a shift in cellular redox balance toward a reduced state. We hypothesized that dichloroacetate (DCA), a metabolic modulator that can shift redox balance(More)
The pulmonary arteries (PA) in pulmonary arterial hypertension (PAH) are constricted and remodeled;. They have suppressed apoptosis, partly attributable to suppression of the bone morphogenetic protein axis and selective downregulation of PA smooth muscle cell (PASMC) voltage-gated K+ channels, including Kv1.5. The Kv downregulation-induced increase in(More)
Pulmonary arterial hypertension (PAH) is characterized by genetic and acquired abnormalities that suppress apoptosis and enhance cell proliferation in the vascular wall, including downregulation of the bone morphogenetic protein axis and voltage-gated K+ (Kv) channels. Survivin is an "inhibitor of apoptosis" protein, previously thought to be expressed(More)
Pulmonary arterial hypertension (PAH) is associated with mutations of bone morphogenetic protein receptor 2 (BMPR2), and BMPR2 expression decreases with the development of experimental PAH. Decreased BMPR2 expression and impaired intracellular BMP signaling in pulmonary artery (PA) smooth muscle cells (PASMC) suppresses apoptosis and promotes proliferation,(More)
Pioglitazone was associated with increased hazard for surgical or percutaneous lower extremity revascularization in patients with diabetes in a large clinical trial, but this clinical finding has not been adequately explored in animal models. We hypothesized that pioglitazone would decrease hypoxia-inducible factor 1α (HIF-1α)-dependent angiogenesis in rat(More)
An aortic aneurysm is characterized by widening of the aortic lumen diameter with adverse remodelling of the vascular extracellular matrix. A thoracic aortic aneurysm (TAA) is highly prevalent in patients with a bicuspid aortic valve (BAV). We investigated the structural remodelling in the aneurysmal ascending aorta in correlation to molecular alterations(More)
This paper demonstrates preliminary in-human validity of a novel subject-specific approach to estimation of central aortic blood pressure (CABP) from peripheral circulatory waveforms. In this “Individualized Transfer Function” (ITF) approach, CABP is estimated in two steps. First, the circulatory dynamics of the cardiovascular system are determined via(More)
For more than a century, it has been known that the body recoils each time the heart ejects blood into the arteries. These subtle cardiogenic body movements have been measured with increasingly convenient ballistocardiography (BCG) instruments over the years. A typical BCG measurement shows several waves, most notably the "I", "J", and "K" waves. However,(More)
This paper presents a novel minimally invasive method for quantifying blood pressure (BP) wave reflection in the arterial tree. In this method, two peripheral BP waveforms are analyzed to obtain an estimate of central aortic BP waveform, which is used together with a peripheral BP waveform to compute forward and backward pressure waves. These forward and(More)