Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Receptor-associated protein (RAP) is a receptor antagonist that inhibits ligand interactions with the receptors that belong to the low density lipoprotein receptor gene family. The low-density lipoprotein receptor-related protein 1 (LRP1) has a crucial role in regulating tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) expression. Furthermore, the functional balance of these two proteins is directly associated with the initiation and development of cerebral ischemic stroke. In the present study, the effect of RAP post-treatment was investigated in a rat autologous thromboembolic model. The expression and activity of t-PA and PAI-1 were detected and the neurological function was tested. The results suggest that post-treatment with RAP is able to improve neurorecovery after ischemic stroke by decreasing vascular damage and regulating t-PA and PAI-1 expressions. Post-treatment with RAP promotes t-PA expression, suppresses PAI-1 expression, significantly improves functional outcomes and decreases the amount of TUNEL-positive cells. RAP-treated rats show lower intracranial hemoglobin levels and a smaller ischemic zone. In conclusion, post-treatment with RAP regulates t-PA and PAI-1 expressions and thereby contributes to the improvement of functional outcomes after cerebral ischemia. Our findings strongly suggest that RAP may be of value in neurorecovery after stroke.
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PMID:Receptor-associated protein promotes t-PA expression, reduces PAI-1 expression and improves neurorecovery after acute ischemic stroke. 2570 49

Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke, important causes of morbidity and mortality across the globe. Abundant epidemiological studies demonstrate that high levels of high density lipoprotein (HDL) are associated with reduced risk of atherosclerosis and preclinical, animal model studies demonstrate that this association is causative. Understanding the molecular mechanisms underlying the protective effects of HDL will allow more strategic approaches to development of HDL based therapeutics. Recent evidence suggests that an important aspect of the ability of HDL to protect against atherosclerosis is its ability to trigger signaling responses in a variety of target cells including endothelial cells and macrophages in the vessel wall. These signaling responses require the HDL receptor, scavenger receptor class B type 1 (SR-B1), an adaptor protein (PDZK1) that binds to the cytosolic C terminus of SR-B1, Akt1 activation and (at least in endothelial cells) activation of endothelial NO synthase (eNOS). Mouse models of atherosclerosis, exemplified by apolipoprotein E or low density lipoprotein receptor gene inactivated mice (apoE or LDLR KO) develop atherosclerosis in their aortas but appear generally resistant to coronary artery atherosclerosis. On the other hand, inactivation of each of the components of HDL signaling (above) in either apoE or LDLR KO mice renders them susceptible to extensive coronary artery atherosclerosis suggesting that HDL signaling may play an important role in protection against coronary artery disease.
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PMID:HDL signaling and protection against coronary artery atherosclerosis in mice. 2664 35

Cardiovascular disease is the leading cause of morbidity and mortality globally, as estimated by the World Health Organization, where in 2016, 15.2 million deaths were attributed to ischemic heart disease and stroke. It is therefore essential to try to reduce the incidence of Cardiovascular disease by controlling modifiable risk factors. One such major modifiable risk factor is cholesterol, which influences the pathogenesis and progression of atherosclerosis. Statins are often prescribed to lower blood levels of low density lipoprotein cholesterol, thereby reducing the risk of Cardiovascular disease by approximately 25-35%. However, there is an increasing number of patients (in particular those with intolerance to statin therapy and those with familial hypercholesterolemia) for whom statin therapy alone is not enough to control low density lipoprotein cholesterol. In this review, the regulation of cholesterol metabolism will be discussed with an emphasis on novel cholesterol lowering drugs used in clinical trials. These second-generation drugs, monoclonal antibodies against the low density lipoprotein receptor gene known as proprotein convertase subtilisin/kexin type 9 inhibitors, are expected to be prescribed to patients who are intolerant to statins, as well as in conjunction with statins. Future perspectives of the clinical use of these drugs is also discussed.
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PMID:A short review of proprotein convertase subtilisin/kexin type 9 inhibitors. 3118 90