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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human umbilical vein endothelial cells (HUVECs) are an endothelial model of replicative senescence. Oxidative stress, possibly due to dysfunctional mitochondria, is believed to play a key role in replicative senescence and atherosclerosis, an age-related vascular disease. In this study, we determined the effect of cell division on genomic instability, mitochondrial function, and redox status in HUVECs that were able to replicate for approximately 60 cumulative population doublings (CPD). After 20 CPD, the nuclear genome deteriorated and the protein content of the cell population increased. This indicated an increase in cell size, which was accompanied by an increase in oxygen consumption, ATP production, and mitochondrial genome copy number and approximately 10% increase in mitochondrial mass. The antioxidant capacity increased, as seen by an increase in reduced glutathione, glutathione peroxidase, GSSG reductase, and glucose-6-phosphate dehydrogenase. However, by CPD 52, the latter two enzymes decreased, as well as the ratio of mitochondrial-to-nuclear genome copies, the mitochondrial mass, and the oxygen consumption per milligram of protein. Our results signify that HUVECs maintain a highly reducing (GSH) environment as they replicate despite genomic instability and loss of mitochondrial function.
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PMID:Endothelial cells maintain a reduced redox environment even as mitochondrial function declines. 1238 90

Endothelial dysfunction (ECD) is the earliest phenotypic change in the vasculature following exposure to atherothrombotic risk factors. ECD is associated with decreased synthesis and increased oxidative inactivation of nitric oxide (NO). Critical antioxidant enzymes essential for eliminating reactive oxygen species that can inactivate NO include the superoxide dismutases, the glutathione peroxidases, catalase, and glucose-6-phosphate dehydrogenase. Deficiencies of these enzymes increase oxidative stress and NO inactivation and, as such, can either lead to ECD or account for the underlying mechanism of ECD associated with a given atherothrombotic risk factor. Selected antioxidants improve intracellular redox state and reverse ECD by improving the bioavailability of NO. These observations provide mechanistic insights into the molecular basis of ECD in vascular disease and its treatment.
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PMID:Oxidative stress in endothelial cell dysfunction and thrombosis. 1367 76

In the vasculature, reactive oxygen species (ROS) generated by both mitochondrial respiration and enzymatic sources serve as integral components of cellular signaling and homeostatic mechanisms. Because ROS are highly reactive biomolecules, the cellular redox milieu is carefully maintained by small-molecule antioxidants and antioxidant enzymes to prevent the deleterious consequences of ROS excess. When this redox balance is perturbed, because of either increased ROS production or decreased antioxidant capacity, oxidant stress is increased in the vessel wall and, if not offset, vascular dysfunction ensues. A number of heritable polymorphisms of pro-oxidant enzymes, including 5-lipoxygenase, cyclooxygenase-2, nitric oxide synthase-3, and NAD(P)H oxidase, have been identified and found to modulate ROS production and, thereby, the risk of atherothrombotic cardiovascular disease in individuals with these genetic polymorphisms. Similarly, heritable deficiency of the antioxidant enzymes catalase, glutathione peroxidases, glutathione-S-transferases, heme oxygenase, and glucose-6-phosphate dehydrogenase favors ROS accumulation, and has been associated with an increased risk of vascular disease. Individually, each of these polymorphisms imposes a state of uncompensated oxidant stress on the vasculature and collectively comprise the oxidative enzymopathies.
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PMID:Oxidative enzymopathies and vascular disease. 1579 Sep 28

Most current theories for the mechanism of hypoxic pulmonary vasoconstriction (HPV) include a role for reactive oxygen species and/or changes in redox regulation, but extreme controversy exists regarding which systems and redox changes mediate the HPV response. Nitric oxide (NO) appears to help to maintain low pulmonary arterial pressure, suppress HPV, and prevent the development of pulmonary hypertension. Our studies have found a key role for glucose-6-phosphate dehydrogenase in bovine pulmonary arterial smooth muscle functioning to maintain elevated levels of cytosolic NADPH which fuels the generation of vasodilator levels of hydrogen peroxide. HPV results from hypoxia removing vasodilation by peroxide. Decreased superoxide generation by Nox4 oxidase and its conversion to peroxide by Cu,Zn-SOD appear to be potential factors in sensing hypoxia, and decreased cGMP-associated vasodilation and removal of redox controlled vasodilator mechanisms by increased cytosolic NADPH may be key coordinators of the HPV response. Oxidant generation associated with vascular disease processes, including the removal of NO by superoxide, and attenuation of its ability to stimulate cGMP production by oxidation of the heme and thiols of soluble guanylate cyclase attenuate potential beneficial actions of NO on pulmonary arterial function. While pulmonary hypertension appears to have multiple poorly understood effects on redox-associated processes, potentially influencing responses to hypoxia and NO-cGMP signaling, much remains to be elucidated regarding how these processes may be important factors in the progression, expression and therapeutic treatment of pulmonary hypertension.
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PMID:Oxidant-redox regulation of pulmonary vascular responses to hypoxia and nitric oxide-cGMP signaling. 2016 May 35

Cellular respiration in an oxygen-rich environment leads to the generation of reactive oxygen species. These partially reduced forms of molecular oxygen can readily react with biological molecules, often modifying their normal biological function. Antioxidant enzyme mechanisms have evolved to eliminate reactive oxygen species and minimize the oxidant stress caused by their reactivity. Inherited and acquired deficiencies of key antioxidant enzymes lead to a dysregulated redox environment, which can promote pathobiology; when this redox dysfunction occurs in the blood vessel, vascular disease ensues. In this article, we consider three distinct antioxidant enzyme deficiencies - glucose-6-phosphate dehydrogenase, glutathione peroxidase-1 and glutathione peroxidase-3 - and their consequences for vascular disease.
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PMID:Antioxidant enzyme deficiencies and vascular disease. 2019 Aug 73