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)

Enhanced blood pressure variability contributes to left ventricular hypertrophy and end-organ damage, even in the absence of hypertension. We hypothesized that the greater number of high-blood pressure episodes associated with enhanced blood pressure variability causes cardiac hypertrophy and dysfunction by activation of mechanosensitive and autocrine pathways. Normotensive mice were subjected to sinoaortic baroreceptor denervation (SAD) or sham surgery. Twelve weeks later, blood pressure variability was doubled in SAD compared with sham-operated mice. Blood pressure did not differ. Cardiac hypertrophy was reflected in greater heart/body weight ratios, larger myocyte cross-sectional areas, and greater left ventricular collagen deposition. Furthermore, left ventricular atrial and brain natriuretic peptide mRNA expression was greater in SAD than in sham-operated mice. SAD had higher left ventricular end-diastolic pressures and lower myocardial contractility indexes, indicating cardiac dysfunction. Cardiac protein content of phosphorylated p125 focal adhesion kinase (p125 FAK) and phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) was greater in SAD than in sham-operated mice, indicating activation of mechanosensitive pathways of cardiac hypertrophy. Furthermore, enhanced cardiac renin and transforming growth factor-beta1 (TGFbeta1) protein content indicates activation of autocrine pathways of cardiac hypertrophy. Adrenal tyrosine hydroxylase protein content and the number of renin-positive glomeruli were not different, suggesting that sympathetic activation and the systemic renin-angiotensin system did not contribute to cardiac hypertrophy. In conclusion, more frequent blood pressure rises in subjects with high blood pressure variability activate mechanosensitive and autocrine pathways leading to cardiac hypertrophy and dysfunction even in the absence of hypertension.
 ...
PMID:Mechanisms of blood pressure variability-induced cardiac hypertrophy and dysfunction in mice with impaired baroreflex. 1556 77

We describe the clinical characteristics of 12 HIV-infected patients who suffered from myocardial infarction (MI) in our clinical cohort. They were compared with a control group matched (1:2) for factors related to cardiovascular risk (age, gender, smoking habit, risk factor for HIV acquisition, hypertension, family history for relevant cardiovascular events, and body mass index) by conditional (fixed-effect) logistic regression analysis. Among patients with MI, 6/12 had never used protease inhibitors (PIs) or were antiretroviral therapy naive. The only variables marginally associated with MI were nadir CD4+ T-cell count <50/mm(3) (odds ratio (OR): 7.2; 95% confidence interval (CI) 0.81-64.2; P: 0.077) and zenith >100,000 HIV RNA copies/mL (OR: 7; 95% CI 0.81-60.2; P: 0.076) at univariate analysis. Moreover, the use of PIs did not result in being associated with the risk of MI. Our data show that in HIV-infected patients, PI use does not seem to have any negative impact on MI while the possible impact of advanced HIV infection itself needs further investigations.
Int J STD AIDS 2005 Jan
PMID:Risk factors for myocardial infarction in HIV-positive patients. 1570 66

The hypertrophy of vascular smooth muscle cells (VSMCs) is critical in vascular remodeling associated with hypertension, atherosclerosis, and restenosis. Recently, leptin has appeared to play a pivotal role in vascular remodeling. However, the mechanism by which leptin induces hypertrophy in vascular smooth muscle cells is still unknown. We studied the role of leptin as a potential hypertrophic factor in rat VSMCs. In the present study, leptin significantly increased [(3)H]leucine incorporation and the total protein/DNA ratio in VSMCs. The maximal hypertrophic effect was at 100ng/ml of leptin. Leptin induced phosphorylation and activation of p38 mitogen-activated protein (p38 MAP) kinase and of signal transducers and activators of transcription 3 in a concentration- and time-dependent manner. A p38 MAP kinase inhibitor SB203580 significantly inhibited leptin-induced hypertrophy, AG490 (a JAK2 inhibitor) partially inhibited it, and other MAP kinase inhibitors, PD98059 (an ERK inhibitor) and SP600125 (a JNK inhibitor), had no effect. These results indicate that leptin directly stimulates cellular hypertrophy via p38 MAP kinase in rat VSMCs.
 ...
PMID:Leptin induces hypertrophy via p38 mitogen-activated protein kinase in rat vascular smooth muscle cells. 1572 Dec 67

The present study evaluated the role of nitric oxide (NO) in the transfer latency (TL) paradigm in the elevated plus-maze. Male Wistar rats received i.p. injections of either 0.9% Saline, N(omega) Nitro-L-arginine-methyl-ester (L-NAME, an inhibitor of NO synthesis), d-NAME (inert isomer), scopolamine (SCO, antagonist of muscarinic receptors), or MK-801 (antagonist of NMDA receptors) and, after 30 min, were submitted to TL procedure. In an independent experiment, the ability of the same L-NAME treatments in changing the arterial pressure and blood glucose level (BGL) was evaluated in conscious rats. The treatment with SCO (1 mg kg(-1)), MK-801 (0.15 mg kg(-1)) and L-NAME (10 and 50 mg kg(-1)), but not with D-NAME, impaired the TL learning. The L-NAME-induced TL deficit was counteracted by L-ARG (100 and 200 mg kg(-1)), while the co-administration of sub-effective doses of L-NAME and MK-801 failed to impair the TL learning. The L-NAME (50 mg kg(-1)) treatment failed to alter the BGL. All treatments with L-NAME induced hypertension, but the rats treated with L-NAME (5 mg kg(-1)) were still able to learn the TL task. The data indicate that the TL deficit induced by L-NAME (10 and 50 mg kg(-1)) is not due to either hypertension or changes in the BGL. It is also possible to establish that NO production is important for emotional learning underlying the TL procedure in rats.
 ...
PMID:The role of nitric oxide in the emotional learning of rats in the plus-maze. 1576 71

Our objective is to analyse patients diagnosed with late-stage HIV infection in the highly active antiretroviral therapy (HAART) area. A prospective, observational study of all patients with an initial CD4 < 50 x 10(6)/L was carried out. Epidemiological, clinical and HAART-associated data were analysed. Survival rates were estimated and pairs of survival curves were compared. The statistical program used was SPSS (version 10). In all, 349 HIV-infected patients were diagnosed, 117 (33.5%) had late-stage disease, mean CD4 23.9 x 10(6)/L and mean viral load (VL) 5.38 log10. In 98 men, mean age 39.5 years, percentage of AIDS cases at their first attendance was 83.8%. The median follow-up period was 28 months and 27 died. Pneumocystis carinii was the most frequent cause of AIDS (24.4%) and death (18.5%). Survival rates at 12, 24 and 36 months were 95.6%, 85.8% and 72.4%. HAART was started in 82.1%. VLs < 50 copies/mL at one, two and three years of treatment were 55.2%, 55.7% and 58.0%. Resource utilization included 0.58 hospitalization/patient/year and 0.07 events/patient/year. HAART-related complications were as follows: 50% lipodystrophy, 9.7% hypertension, 22.2% hyperglycaemia, 26.4% hypercholesterolaemia, 31.9% hypertrygliceridaemia and 18.1% mixed hyperlipaemia. Over one-third of our patients have advanced HIV infection at diagnosis. However, the outcome is favourable, with a good immunovirological response and few new opportunistic events. HAART-related complications were frequent.
Int J STD AIDS 2005 Mar
PMID:Study of patients diagnosed with advanced HIV in the HAART era--OMEGA Cohort. 1582 28

Dynamic remodeling of the actin cytoskeleton occurs during agonist-induced smooth muscle contraction. Tyrosine phosphorylation of the adaptor protein paxillin has been implicated in regulation of actin filament formation and force development. We have investigated the role of the actin cytoskeleton in noradrenaline (NA)-induced and endothelin (ET)-induced activation of the calcium-dependent nonreceptor tyrosine kinase PYK2 and subsequent phosphorylation of paxillin in rat small mesenteric arteries. NA and ET induced a rapid and prolonged activation of PYK2, as shown by increased phosphorylation at Y402 and Y881, and a concomitant association of the kinase with a Triton X-100 insoluble membrane (cytoskeleton) compartment. Both agonists also increased phosphorylation of paxillin at Y31 and Y118 with a similar time course as PYK2 phosphorylation, and induced its association with the same membrane compartment as PYK2. Treatment of arteries with cytochalasin D disrupted stress fibers and inhibited NA-induced and ET-induced force in a myosin light chain 20 phosphorylation independent and reversible manner. However, cytochalasin D treatment had no effect on NA-induced and ET-induced phosphorylation of either PYK2 or paxillin but did prevent their association with the TritonX-100 insoluble membrane compartment. These results show that in mesenteric arteries an intact cytoskeleton and force development are not prerequisites for G-protein--coupled receptor--induced activation of PYK2 and paxillin, by tyrosine phosphorylation, in vascular tissue, but are necessary for the translocation of PYK2 and paxillin to the membrane.
Hypertension 2005 Jul
PMID:Role of the actin cytoskeleton in G-protein-coupled receptor activation of PYK2 and paxillin in vascular smooth muscle. 1591 46

Despite of several lines of evidence indicating a pathophysiologic role of platelets in pulmonary hypertension, the occurrence of chronic endogenous platelet activation has been a matter of debate. It was hypothesized that the pattern of tyrosine phosphorylation of platelet proteins examined ex vivo could provide information on the state of platelet activation. This was examined in 10 patients with pulmonary arterial hypertension aged 18 to 53 years. Phosphotyrosine density and the amounts of specific proteins were analyzed in resting platelets after reaction with anti-phosphotyrosine, anti-pp60(s-src), anti-pp125(FAK), and anti-alphaIIbbeta3 antibodies. There was a 79% increase in protein-associated phosphotyrosine in patients in comparison to levels in controls (p<0.05). In particular, phosphorylation on tyrosine residues of pp120 and pp125(FAK) increased 24% and 57%, respectively (p<0.05). Although pp60(s-src)-associated phosphotyrosine was not altered in the patient group as a whole, it was clearly decreased in three subjects. Platelet content of beta3 integrin, pp60(s-src), and pp125(FAK), was not altered. This pattern of phosphorylation suggests an ongoing process of platelet activation. Because phosphorylation of pp125(FAK) is a late, integrin-dependent event, results suggest that platelet activation and aggregation occur in vivo in these patients.
 ...
PMID:Increased tyrosine phosphorylation of platelet proteins including pp125(FAK) suggests endogenous activation and aggregation in pulmonary hypertension. 1624 66

They were more than just another kinases (JAK), when they were first described in the late 80s and named JAK kinases. The mandatory role of this novel family of dual active janus kinases (JAK) and their substrates the signal transducers and activators of transcription (STAT) was demonstrated in mice who died during embryogenesis when lacking a functional allele, e.g. that of JAK2. Initially, the JAK/STAT signaling pathway was discovered as the primary mediator of intracellular signaling induced by interferon in hematopoietic and immune cells. Nowadays, it is well accepted that JAK kinases and STAT proteins are constitutively expressed in the vessel wall in a cell type specific manner and transfer intracellular signaling events of various receptor families, e.g. that of cytokines, growth factors and vasoactive peptides such as angiotensin II (Ang II) or endothelin. The potential impact of the JAK/STAT signaling pathway on cardiovascular pathophysiology and disease development arise from reports describing that JAKs may bind directly to the angiotensin II type I (AT(1)) receptor, thereby enhancing their phosphorylation in various cell types of the vessel wall. More interestingly, these signaling events are modulated by NAD(P)H oxidase-derived superoxide anions which directly phosphorylate JAK2 and thereby control JAK2 activity. A potential impact was also described for atherosclerotic plaque development in which the activation of JAKs and STATs seems to be critical. Based on these observations, we here review the role of the JAK/STAT signaling pathways as critical regulator for cardiovascular disease development, i.e. atherosclerotic plaque progression or the manifestation of arterial hypertension.
 ...
PMID:JANUS under stress--role of JAK/STAT signaling pathway in vascular diseases. 1627 17

Accumulating evidence strongly implicates angiotensin II (AngII) intracellular signaling in mediating cardiovascular diseases such as hypertension, atherosclerosis and restenosis after vascular injury. In vascular smooth muscle cells (VSMCs), through its G-protein-coupled AngII Type 1 receptor (AT(1)), AngII activates various intracellular protein kinases, such as receptor or non-receptor tyrosine kinases, which includes epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), c-Src, PYK2, FAK, JAK2. In addition, AngII activates serine/threonine kinases such as mitogen-activated protein kinase (MAPK) family, p70 S6 kinase, Akt/protein kinase B and various protein kinase C isoforms. In VSMCs, AngII also induces the generation of intracellular reactive oxygen species (ROS), which play critical roles in activation and modulation of above signal transduction. Less is known about endothelial cell (EC) AngII signaling than VSMCs, however, recent studies suggest that endothelial AngII signaling negatively regulates the nitric oxide (NO) signaling pathway and thereby induces endothelial dysfunction. Moreover, in both VSMCs and ECs, AngII signaling cross-talk with insulin signaling might be involved in insulin resistance, an important risk factor in the development of cardiovascular diseases. In fact, clinical and pharmacological studies showed that AngII infusion induces insulin resistance and AngII converting enzyme inhibitors and AT(1) receptor blockers improve insulin sensitivity. In this review, we focus on the recent findings that suggest the existence of novel signaling mechanisms whereby AngII mediates processes, such as activation of receptor or non-receptor tyrosine kinases and ROS, as well as cross-talk between insulin and NO signal transduction in VSMCs and ECs.
 ...
PMID:Angiotensin II regulates vascular and endothelial dysfunction: recent topics of Angiotensin II type-1 receptor signaling in the vasculature. 1647 78

This study was carried out to build statistical models for defining FGR (Fetal Growth Restriction) in weight and/or length after taking growth potential of an infant into account. From a cohort of pregnant women having given birth to 47,733 infants in 141 French maternity units, two statistical models gave individualized limits of birth weight and birth length (based on the 5th centile) below which, after adjustment for its individual growth potential, a newborn must be considered as FGR in weight and/or in length. A sample of 906 infants had measures taken of cord blood growth factors (IGF1, IGFBP3). The FGR(W) definition (weight<5th centile for growth potential) permitted the identification of infants who presented rates of maternal hypertension (13.6%) and of Apgar score at 5 min<6 (2.9%) higher than in the classical group SGA(W) (weight<5th centile for sex and gestational age) (9.6% and 2.2% respectively). By combining FGR(W) and SGA(W), a subgroup of infants, not currently recognized as SGA, presented very high rates of maternal hypertension (19.9%) and of low Apgar score (3.9%). Conversely a subgroup of infants, currently recognized as SGA(W), had rates as low as in the normal infants group, and had to be considered as "constitutionally small" (that is to say 24% of the SGA(W)). Combining FGR(W) and FGR(L) (length<5th centile of growth potential), 7.6% of infants appeared growth-restricted, and 1.8% appeared constitutionally small in weight and/or in length. The FGR(W)-FGR(L) infants showed the lowest mean values of IGF1 (126.2+/-3.2) and IGFBP3 (0.86+/-0.03). These new definitions of FGR(W) and FGR(L) could help to better identify infants at birth requiring neonatal care, and monitoring of growth catch-up and neurodevelopmental outcome.
 ...
PMID:Identification of newborns with Fetal Growth Restriction (FGR) in weight and/or length based on constitutional growth potential. 1683 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>