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Metabolism and Redox in Pulmonary Vascular Physiology and Pathophysiology.

ABSTRACT: Significance: This review considers how some systems controlling pulmonary vascular function are potentially regulated by redox processes to examine how and why conditions such as prolonged hypoxia, pathological mediators, and other factors promoting vascular remodeling contribute to the development of pulmonary hypertension (PH). Recent Advances and Critical Issues: Aspects of vascular remodeling induction mechanisms described are associated with shifts in glucose metabolism through the pentose phosphate pathway and increased cytosolic NADPH generation by glucose-6-phosphate dehydrogenase, increased glycolysis generation of cytosolic NADH and lactate, mitochondrial dysfunction associated with superoxide dismutase-2 depletion, changes in reactive oxygen species and iron metabolism, and redox signaling. Future Directions: The regulation and impact of hypoxia-inducible factor and the function of cGMP-dependent and redox regulation of protein kinase G are considered for their potential roles as key sensors and coordinators of redox and metabolic processes controlling the progression of vascular pathophysiology in PH, and how modulating aspects of metabolic and redox regulatory systems potentially function in beneficial therapeutic approaches.

SUBMITTER: Alruwaili N

PROVIDER: S-EPMC6708269 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Metabolism and Redox in Pulmonary Vascular Physiology and Pathophysiology.

Alruwaili Norah N Kandhi Sharath S Sun Dong D Wolin Michael S MS

Antioxidants & redox signaling 20181221 10

Significance: This review considers how some systems controlling pulmonary vascular function are potentially regulated by redox processes to examine how and why conditions such as prolonged hypoxia, pathological mediators, and other factors promoting vascular remodeling contribute to the development of pulmonary hypertension (PH). Recent Advances and Critical Issues: Aspects of vascular remodeling induction mechanisms described are associated with shifts in glucose me ...[more]

PMID: 30403147

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Project description:Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical applications of leptin or its analogs in human therapeutics.

Dataset Information

Metabolism and Redox in Pulmonary Vascular Physiology and Pathophysiology.

Publications

Metabolism and Redox in Pulmonary Vascular Physiology and Pathophysiology.

Similar Datasets

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