Circulation research
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Circulation research · Apr 2013
Hypoxia-inducible factor-1α in pulmonary artery smooth muscle cells lowers vascular tone by decreasing myosin light chain phosphorylation.
Hypoxia-inducible factor-1α (HIF-1α), an oxygen (O2)-sensitive transcription factor, mediates transcriptional responses to low-O2 tension states. Although acute hypoxia causes pulmonary vasoconstriction and chronic hypoxia can cause vascular remodeling and pulmonary hypertension, conflicting data exist on the role of HIF-1α in modulating pulmonary vascular tone. ⋯ In both normoxia and hypoxia, PASMC HIF-1α maintains low pulmonary vascular tone by decreasing myosin light chain phosphorylation. Compromised PASMC HIF-1α expression may contribute to the heightened vasoconstriction that characterizes pulmonary hypertension.
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Circulation research · Apr 2013
Discovery and characterization of alamandine: a novel component of the renin-angiotensin system.
The renin-angiotensin system (RAS) is a key regulator of the cardiovascular system, electrolyte, and water balance. Here, we report identification and characterization of alamandine, a new heptapeptide generated by catalytic action of angiotensin-converting enzyme-2 angiotensin A or directly from angiotensin-(1-7). ⋯ The identification of these 2 novel components of the RAS, alamandine and its receptor, provides new insights for the understanding of the physiological and pathophysiological role of the RAS and may help to develop new therapeutic strategies for treating human cardiovascular diseases and other related disorders.
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Circulation research · Apr 2013
Chloroquine prevents progression of experimental pulmonary hypertension via inhibition of autophagy and lysosomal bone morphogenetic protein type II receptor degradation.
Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation and apoptosis resistance in pulmonary artery smooth muscle cells (PASMCs). ⋯ Chloroquine and hydroxychloroquine exert beneficial effects in experimental PAH. The mechanism of action includes inhibition of autophagy pathways and inhibition of lysosomal degradation of BMPR-II.