Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension causes vascular changes of essentially three types: structurally adaptative changes, degenerative alterations unrelated to atherosclerosis, and atherosclerosis. Structural changes result in an increased peripheral resistance, even in the relaxed vascular bed, and a reduced collateral capacity, thus predisposing to ischemia distal to an arterial stenosis/occlusion and to "watershed" infarcts in connection with a drop in blood pressure. Degenerative changes in the small intracerebral arteries can lead to plasma extravasation and focal brain edema, lacunar infarcts, and intracerebral hemorrhages. Hypertension also predisposes to saccular aneurysms and subarachnoid hemorrhages. Finally, atherosclerotic changes including stenoses or occlusions of predominantly extracranial and pial arteries give rise to transitory ischemic attacks and brain infarcts by artery-to-artery embolism or distal hemodynamic perfusion insufficiency.
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PMID:Vascular mechanisms in hypertensive cerebrovascular disease. 137 27

Reactive oxygen species (ROS) have been implicated in the pathogenesis of many clinical disorders such as adult respiratory distress syndrome, ischemia-reperfusion injury, atherosclerosis, neurodegenerative diseases, and cancer. Genetically engineered animal models have been used as a tool for understanding the function of various antioxidant enzymes in cellular defense mechanisms against various types of oxidant tissue injury. Transgenic mice overexpressing three isoforms of superoxide dismutase, catalase, and the cellular glutathione peroxidase (GSHPx-1) in various tissues show an increased tolerance to ischemia-reperfusion heart and brain injury, hyperoxia, cold-induced brain edema, adriamycin, and paraquat toxicity. These results have provided for the first time direct evidence demonstrating the importance of each of these antioxidant enzymes in protecting the animals against the injury resulting from these insults, as well as the effect of an enhanced level of antioxidant in ameliorating the oxidant tissue injury. To evaluate further the nature of these enzymes in antioxidant defense, gene knockout mice deficient in copper-zinc superoxide dismutase (CuZnSOD) and GSHPx-1 have also been generated in our laboratory. These mice developed normally and showed no marked pathologic changes under normal physiologic conditions. In addition, a deficiency in these genes had no effects on animal survival under hyperoxida. However, these knockout mice exhibited a pronounced susceptibility to paraquat toxicity and myocardial ischemia-reperfusion injury. Furthermore, female mice lacking CuZnSOD also displayed a marked increase in postimplantation embryonic lethality. These animals should provide a useful model for uncovering the identity of ROS that participate in the pathogenesis of various clinical disorders and for defining the role of each antioxidant enzyme in cellular defense against oxidant-mediated tissue injury.
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PMID:The nature of antioxidant defense mechanisms: a lesson from transgenic studies. 978 1

Neurovascular remodeling has been recently recognized as a promising target for neurologic therapies. Hopes have emerged that, by stimulating vessel growth, it may be possible to stabilize brain perfusion, and at the same time promote neuronal survival, brain plasticity, and neurologic recovery. In this review, we outline the role of vascular endothelial growth factor (VEGF) in the ischemic brain, analyzing how this growth factor contributes to brain remodeling. Studies with therapeutic VEGF administration resulted in quite variable results depending on the route and time point of delivery. Local VEGF administration consistently enhanced neurologic recovery, whereas acute intravenous delivery exacerbated brain infarcts due to enhanced brain edema. Future studies should answer the following questions: (1) whether increased vessel density translates into improvements in blood flow in the hemodynamically compromised brain; (2) how VEGF influences brain plasticity and contributes to motor and nonmotor recovery; (3) what are the actions of VEGF not only in young animals with preserved vasculature, on which previous studies have been conducted, but also in aged animals and in animals with preexisting atherosclerosis; and (4) whether the effects of VEGF can be mimicked by pharmacological compounds or by cell-based therapies. Only on the basis of such information can more definite conclusions be made with regard to whether the translation of therapeutic angiogenesis into clinics is promising.
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PMID:Implications of vascular endothelial growth factor for postischemic neurovascular remodeling. 1965 90

Endothelial calcium/calmodulin-gated K channels of small (KCa2.3) and intermediate conductance (KCa3.1) produce membrane hyperpolarization and endothelium-dependent hyperpolarization (EDH)-mediated vasodilation. Dysfunctions of the two channels and ensuing EDH impairments are found in several cardiovascular pathologies such as diabetes, atherosclerosis, postangioplastic neointima formation, but also inflammatory disease, cancer, and organ fibrosis. Moreover, KCa3.1 plays an important role in endothelial barrier dysfunction, edema formation in cardiac and pulmonary disease, and in ischemic stroke. Concerning KCa2.3, genome-wide association studies revealed an association of KCa2.3 channels with atrial fibrillation in humans. Accordingly, both channels are considered potential drug targets for cardio- and cerebrovascular disease states. In this chapter, we briefly review the function of the two channels in EDH-type vasodilation and systemic circulatory regulation and then highlight their pathophysiological roles in ischemic stroke as well as in pulmonary and brain edema. Finally, the authors summarize recent advances in the pharmacology of the channels and explore potential therapeutic utilities of novel channel modulators.
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PMID:Endothelial Small- and Intermediate-Conductance K Channels and Endothelium-Dependent Hyperpolarization as Drug Targets in Cardiovascular Disease. 2745 Oct 95

The chapter describes the epidemiology of cerebrovascular diseases, anatomy of the cerebral blood vessels, pathophysiology of ischemia, hypoxia, hypoxemia, anemic hypoxia, histotoxic hypoxia, carbon monoxide damage, hyperoxid brain damage and decompression sickness, and selective cell and regional vulnerability; diseases of the blood vessels including atherosclerosis, hypertensive angiopathy, small vessel disease, inflammatory vascular diseases, cerebral amyloid angiopathies, CADASIL, CARASIL and other diseases that can lead to cerebrovascular occlusion; intracranial and intraspinal aneurysms and vascular malformations; hematologic disorders that can cause cerebral infarct or hemorrhage; brain ischemic damage; and spontaneous intracranial bleeding. Within ischemic brain damage, focal cerebral ischemia, hemorrhagic infarct, brain edema, penumbra, global cerebral ischemia, venous thrombosis, lacunas and lacunar state, status cribosus, granular atrophy of the cerebral cortex, hippocampal sclerosis, vascular leukoencephalopathy Binswanger type and multi-infarct encephalopathy are discussed in detail. Cognitive impairment of vascular origin deserves an individual section.
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PMID:Neuropathology of cerebrovascular diseases. 2898 97

The incidence of traumatic brain injury (TBI) has been increasing annually. Annexin A7 is a calcium-dependent phospholipid binding protein. It can promote melting of the cell membrane. Recent studies have shown that it plays an important role in atherosclerosis, other cardiovascular diseases, and a variety of tumors. However, few studies of ANXA7 in TBI have been performed. We here observed how ANXA7 changes after TBI and discuss whether brain injury is associated with the use of ANXA7 antagonist intervention. Experimental Results: 1. After TBI, ANXA7 levels were higher than in the sham group, peaking 24 h after TBI. 2. The use of siA7 was found to reduce the expression of A7 in the injured brain tissue, and also brain edema, BBB damage, cell death, and apoptosis relative to the sham group. Conclusion: ANXA7 promotes the development of secondary brain injury (SBI) after TBI.
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PMID:Annexin A7 Levels Increase in Rats With Traumatic Brain Injury and Promote Secondary Brain Injury. 2989 83