Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, the binding of renin and prorenin to cellular receptors with the subsequent generation of second messengers and the production of physiological effects has been demonstrated. In addition, the internalization of prorenin by target cells has been associated with increased cellular synthesis of angiotensin and cardiac pathology. Also, a renin transcript lacking the sequences encoding a secretory signal has been reported, and this transcript appears to produce a renin that acts in the cell that synthesized it. Some years ago, we coined the term intracrine for a peptide hormone or factor that acts in the intracellular space either after internalization or retention in its cell of synthesis. Thus defined, a wide variety of peptides display intracrine functionality, including hormones, growth factors, transcription factors, and enzymes. For example, considerable evidence indicates that angiotensin II is an intracrine. Also, general principles of intracrine functionality have been developed. Thus, recent evidence demonstrates that the prorenin/renin molecule is an intracrine enzyme. Here, the actions of intracrine enzymes (angiogenin, phosphoglucose isomerase, phospholipase A2, granzyme A and B, thioredoxin, platelet-derived endothelial growth factor, and serine protease inhibitors) are reviewed. The relation of prorenin/renin to other intracrine enzymes, and to intracrines in general, is discussed.
Hypertension 2003 Aug
PMID:Intracellular renin and the nature of intracrine enzymes. 1286 Aug 32

Atherosclerosis is the leading cause of death in patients with diabetes mellitus, increasing mortality in all forms of the disease. Classical risk factors, including hyperlipidemia, hypertension and obesity, do not completely account for the increased incidence of atherosclerosis in diabetes. Some platelet activation markers such as CD62P, CD63, PAC-1, Annexin V and platelet-derived microparticles (PDMP) are elevated in patients with diabetes, since diabetic platelets often have increased sensitivity to secondary aggregation in response to agonist. PDMPs are thought to play a role in clinical disease because they express phospholipids that function as procoagulants. High shear stress can initiate both platelet aggregation and shedding of procoagulant-containing PDMP, suggesting that PDMP generation by high shear stress occurs in small diseased arteries and arterioles under various clinical conditions. Platelet activation markers were significantly higher in the hypertensive or hyperlipidemic patients than in the controls. Selectins and cell adhesion molecules were also higher in the hypertensive or hyperlipidemic patients, and they were significantly higher in these patients with diabetes. Activated microparticles and PDMP may contribute to the development of atherosclerosis in diabetes, and platelet activation markers seem to be useful for the assessment of vascular damage in these patients.
 ...
PMID:[Platelet activation marker]. 1467 88

Delayed cerebral ischemia as a result of cerebral vasospasm is the most common cause of death and disability after aneurysmal subarachnoid hemorrhage (SAH). It leads to death or permanent neurologic deficits in over 17-40% of SAH patients. The initial and main symptom of cerebral vasospasm is diffuse headache and may be accompanied with a slight increase in discomfort from neck stiffness and fever. The clinical diagnosis of cerebral vasospasm is made when the patient experiences an altered level of consciousness or a new focal neurologic deficit. There has been a great progress in identifying the patients at risk, putative mechanisms, and possible treatment options for cerebral vasospasm. However, the problem is by no means solved, mainly due to a limited understanding of the pathologic mechanisms of this complex disease. The iatrogenic factors that can increase the risk of cerebral vasospasm include prolongation of the subarachnoid clot by antifibrinolytic drugs, hypotension, inappropriate treatment of hyponatremia, hypovolemia, hyperthermia and increased intracranial pressure. Nimodipine has been shown to improve neurologic outcome and decrease the incidence of cerebral vasospasm. Triple H therapy is a treatment designed to augment cerebral blood flow for patient with cerebral vasospasm. Hypervolemic hypertension is induced with intravenous volume expansion with crystalloid or colloid to increase cardiac output and raise blood pressure. However, small randomized trials showed no clear benefit. Recently, balloon and chemical angioplasty with superselective intra-arterial injection of vasodilators has emerged as the primary intervention for treating medically refractory ischemia from cerebral vasospasm and in many centers is being used as a first-line treatment or even prophylactically. In addition, promising new treatments for cerebral vasospasm or its ischemic complications include magnesium sulfate, fasudil hydrochloride, tirilazad mesylate, erythropoietin, and induced hypothermia; however, all still need further clinical trials. Newly recognized mediators of cerebral vasospasm after SAH include endothelium-derived mediators, vascular smooth-muscle-derived mediators, proinflammatory mediators involved in blood-brain barrier disruption, cytokines and adhesion molecules, stress-induced gene activation, and platelet-derived growth factors. Moreover, observations in the laboratory have, in many circumstances, matched those of reported small series. Larger, prospective, randomized trials are needed to verify several hypotheses of molecular pathophysiology and clinical treatment regimens.
 ...
PMID:Treatment of cerebral vasospasm after subarachnoid hemorrhage--a review. 1567 31

This review addresses a rapidly growing area of vascular biology, i.e. genomic variations in vascular genes that underlie different human phenotypes. Two of the most important molecular in vascular biology, endothelial nitric oxide synthase (eNOS) and vascular endothelial cell growth factor (VEGF)are discussed. Variations in the eNOS gene have been correlated with a number of human diseases including hypertension, coronary vasospasm, smoking dependent risk of coronary disease, myocardial infarction and placental disruption. Similarly, variations in the VEGF gene have been associated with increased risk of various cancers, DiGeorge syndrome, psoriasis, diabetic renal disease and amyotropic lateral sclerosis. Understanding the molecular basis of these genetic variations and how they contribute to the pathophysiology provides new and important insights into human disease.
 ...
PMID:Genetic variations in vascular endothelial growth factor and endothelial nitric oxide synthase and their contributions to human disease. 1582 52

Platelets express the endothelial form of the nitric oxide synthase (eNOS) and generate NO. However, in contrast to eNOS in endothelial cells, eNOS in platelets is largely Ca(2+)-independent and the activity is regulated by phosphorylation. Platelet-derived NO plays an important role in the regulation of platelet aggregation and secretion. Changes in the activity of platelet eNOS are responsible for the abnormal platelet activation encountered in different pathological situations (e.g. hypertension and diabetes). In this review, we will summarize the current knowledge of the role of platelet eNOS and the regulation of its activity as well as the fate of platelet-derived NO in physiological and pathological situations.
 ...
PMID:Endothelial nitric oxide synthase (eNOS) in platelets: how is it regulated and what is it doing there? 1641 87

Nifedipine, a dihydropyridine calcium antagonist, improves endothelial function in patients with hypercholesterolaemia by enhancing nitric oxide (NO) activity, and increases endothelial NO bioavailability by antioxidant mechanisms. We administered a long-acting nifedipine formulation (controlled release (CR) nifedipine: 20 mg/day) to hypertensive patients for 6 months. There were no other changes of drug treatment during therapy with CR nifedipine. Clinical and biochemical data obtained before and after CR nifedipine administration were compared. All markers were measured by enzyme-linked immunosorbant assay. The levels of soluble markers (soluble CD40 ligand, soluble P-selectin, and soluble E-selectin), microparticles (MP) (platelet-derived MP, monocyte-derived MP, and endothelial cell-derived MP), and adiponectin differed between the control group and the hypertension group. The levels of these markers were also different in hypertensive patients with and without type 2 diabetes compared with the control group. In the hypertensive patients with type 2 diabetes, all markers except adiponectin decreased significantly after 3 months of CR nifedipine treatment. In contrast, markers were unchanged in the hypertensive patients without type 2 diabetes. Adiponectin was increased after 6 months of CR nifedipine treatment in hypertensive patients with type 2 diabetes. The effects of CR nifedipine on platelet/monocyte activation and adiponectin levels demonstrated in the present study indicate the potential effectiveness of calcium antagonist therapy for hypertensive patients with type 2 diabetes.
 ...
PMID:Effect of nifedipine on adiponectin in hypertensive patients with type 2 diabetes mellitus. 1706 83

The arterial vessel wall response to a variety of injuries consists in structural changes, which can result in luminal narrowing and aggravation of the underlying disease. This arterial remodeling is characterized by neointima formation and medial thickening, inflammatory cell recruitment and endothelial dysfunction. Chemokines and the corresponding receptors have been shown to participate at every step of the remodeling process. The monocyte chemotactic protein (MCP)-1/CC motif receptor 2 (CCR2) axis induces monocyte infiltration of the injured vessel wall and can stimulate proliferation of smooth muscle cells (SMCs) in models of restenosis, cardiac allograft vasculopathy (CAV), pulmonary hypertension, and systemic hypertension. In contrast, stromal cell-derived factor (SDF)-1 alpha and its receptor CXC motif receptor 4 (CXCR4) are centrally involved in the neointimal recruitment of SMC progenitor cells (SPCs), presumably in response to SMC apoptosis, in restenosis and CAV. The RANTES (Regulated upon activation, normally T-cell expressed, and presumably secreted) receptors CC motif receptor 1 (CCR1) and CC motif receptor 5 (CCR5) affect intimal monocyte infiltration and neointimal growth, which could be due to the deposition of platelet-derived RANTES on activated endothelial cells. Fractalkine is expressed on neointimal SMCs and thus mediates the arrest of monocytes. Interestingly, reendothelialization of injured vessels appears to primarily depend on CXC motif ligand 1 (CXCL1). These chemokine effects form a complex network, which operates in all mechanisms of vascular remodeling. The detailed understanding of the function of the chemokine network in the remodeling process may allow specific disease intervention.
 ...
PMID:Chemokines in vascular remodeling. 1747 83

Three patients with advanced renal-cell cancer were treated with sunitinib 50 mg daily for 4 weeks followed by a rest period of 2 weeks because of progressive disease. The first patient developed stomatitis and a painful blister on his foot. Complaints disappeared after temporary discontinuation of treatment. Re-treatment at a lower dosage was successful until disease progression. The second patient developed skin discolouration, fatigue, fever and diarrhoea. After treatment was interrupted shortly, these symptoms disappeared and sunitinib was recommenced at a lower dosage. The patient went on to develop stomatitis, thrombocytopenia and hypertension (treated with amlodipine). She subsequently had hand-foot syndrome. She died due to brain metastases. In the third patient symptoms of disease returned during the rest period, because of which he received a reduced dosage of sunitinib on a continuous base. He developed diarrhoea which disappeared after a short interruption of the drug. Sunitinib has been approved for the treatment of advanced renal-cell cancer and imatinib-resistant gastro-intestinal stromal tumours. This novel targeting molecule is a tyrosine-kinase inhibitor of vascular endothelial growth-factor receptors, platelet-derived growth-factor receptors and c-Kit. It can induce adverse events that differ from those observed in treatment with conventional cytotoxic agents. The adverse effects are reduced by lowering the dosage and in the rest period within the treatment cycle.
 ...
PMID:[Adverse effects of the tyrosine-kinase inhibitor sunitinib, a new drug for the treatment of advanced renal-cell cancer]. 1755 72

Nitric oxide (NO) inhibits platelet function and plays a key role in the regulation of cardiovascular homeostasis. Essential hypertension is characterized by an increased risk of thrombus formation, and by an inhibition of intraplatelet NO bioactivity. We have previously shown that membrane transport of L-arginine is a rate-limiting step for platelet-derived NO synthesis. This study examined the effects of exercise on the platelet L-arginine-NO pathway and aggregation and systemic inflammation markers in 13 sedentary hypertensive patients subjected to 60 min of training activity (exercise group), predominantly aerobic, three times a week for a period of 12 weeks. Six sedentary hypertensive patients participated in the control group. After 12 weeks, L-arginine transport was significantly increased and associated with increased platelet NO synthase activity and cGMP levels and reduced platelet aggregation. Moreover, exercise training reduced plasma concentrations of fibrinogen and C-reactive protein and blood pressure. The control group did not change their previous intraplatelet L-arginine-NO results and systemic inflammatory markers levels. Thus, exercise training reduces inflammatory responses, restores NO synthesis in platelets and thereby contributes to the beneficial effects of exercise in hypertension. The present study adds exercise as a new tool to reduce morbidity and mortality associated with platelet activation in hypertension.
 ...
PMID:Chronic exercise reduces platelet activation in hypertension: upregulation of the L-arginine-nitric oxide pathway. 1824 41

The last 10 years have seen significant advances in the understanding of the pathophysiology and treatment of pulmonary arterial hypertension (PAH). This has included new insights into the genetics, cell-signalling pathways and pathological changes seen in the small pulmonary arteries as well as the introduction of new treatments which have improved prognosis. The classification of pulmonary hypertension (PH) has also been changed several times, most recently in 2003. It now divides forms of PH into 5 broad groups according to their pathophysiology and response to treatment. This review focuses primarily on the advances that have been made in the comprehension and treatment of Group 1 (PAH); however reference is also made to other groups within the classification. Pharmacologic treatment now includes calcium-channel blockers, endothelin antagonists, prostanoids, phosphodiesterase type 5 inhibitors, anticoagulants and diuretics. There are 2 recent sets of guidelines directing treatment, one published by the American College of Chest Physicians in 2007 and the most recent published by the National Pulmonary Hypertension Centres of the UK and Ireland in 2008. The recent advances in understanding of the underlying cellular mechanisms have also opened the doorway to new potential therapies such as stem cell transplantation and the targeting of platelet-derived factors and apoptosis.
 ...
PMID:Pulmonary arterial hypertension. 1948 26


<< Previous 1 2 3 4 5 Next >>