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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognosis for patients with human immunodeficiency virus (HIV) infection has improved remarkably as a result of effective antiretroviral therapy. This has resulted in an increased awareness of cardiac complications from HIV infection, including cardiomyopathy and overt heart failure. Mechanisms responsible for HIV cardiomyopathy and heart failure are unknown, but may include direct effects of HIV proteins on the heart. We have previously reported that the HIV envelope glycoprotein, gp120, has a p38 MAP kinase-dependent negative inotropic effect on adult rat ventricular myocytes (ARVM). This signaling pathway presumably results from the binding of gp120 to a specific receptor on the surface of cardiac myocytes. HIV gp120 has been shown to bind to CD4, CXCR4, and CCR5 receptors on lymphocytes and macrophages. Accordingly, we sought to determine if HIV gp120 regulated its negative inotropic effect through activation of one of these binding sites on cardiac myocytes. AMD3100, a highly selective CXCR4 receptor antagonist, reversed HIV gp120-induced negative inotropic effect on ARVM. AMD3100 also blocked HIV gp120 phosphorylation of both p38 MAP kinase and Troponin I. The binding of gp120 to the CXCR4 receptor on ARVM was confirmed by co-immunoprecipitation. We conclude that the negative inotropic effect of HIV gp120 is mediated by a novel signaling pathway that begins with binding to a cardiac myocyte CXCR4 receptor, followed by phosphorylation of both p38 MAP kinase and Troponin I.
Cardiovasc Toxicol 2008 Dec
PMID:CXCR4 receptor antagonist blocks cardiac myocyte p38 MAP kinase phosphorylation by HIV gp120. 1885 76

In HIV infected patients an increased occurence of cardiac events has been demontrated from the introduction of highly active antiretroviral therapy (HAART). Antiretroviral drugs' regimens are, in fact, associated with several metabolic side effects, such as dyslipidemia, impaired glucose metabolism and abnormal body fat distribution, that increase the cardiovascular risk of HIV subjects. In addition, HIV infection itself, the chronic inflammatory status and the relevant presence in this population of some of the traditional cardiovascular risk factors contribute to an higher incidence of cardio and cerebrovascular events. In last years several studies showed the occurence of carotid vascular impairment in patients in treatment with protease inhibitors (PI). Similarly the DAD Study reported an increase of 26% of the risk of myocardial infarction in patients on HAART and that this risk is indipendently associated with longer exposure to PI, even after multivariate adjustments. A correct evaluation of the metabolic status before starting HAART and an adeguate control of the drugs-related metabolic abnormalities may reduce the incidence of cardiac events and still improve HIV patients prognosis. This review will focus on the metbolic effects of antiretroviral drugs and to the contribution of combination antiretroviral therapy on cardiovascular risk.
Cardiovasc Hematol Disord Drug Targets 2008 Dec
PMID:Cardiovascular effects of antiretroviral drugs: clinical review. 1907 33

The pericardium, myocardium, coronary arteries and pulmonary arteries are the main targets for cardiac disease in people who are infected with HIV. Geography and access to highly active anti-retroviral therapy (HAART) have a major influence on which of these targets is affected. In sub-Saharan Africa, where tuberculosis is endemic and access to HAART is limited, the dominant forms of HIV-associated heart disease are pericardial tuberculosis and cardiomyopathy. However, in industrialized countries, where tuberculosis is rare and HAART is widely available, coronary artery disease is the main cause of death and disability in these patients. Observational data suggest that HAART, by preserving immune function, reduces the incidence of myopericardial disease and pulmonary hypertension. The result has been that, although optimal strategies to reduce vascular disease in this population continue to be sought and debated in industrialized nations, the focus of prevention and treatment strategies for HIV-related heart disease in developing countries has been to support the active campaigns to get universal access to HAART in the first place. Herein, we review the cardiac manifestations of HIV in sub-Saharan Africa.
Nat Clin Pract Cardiovasc Med 2009 Feb
PMID:Cardiac manifestations of HIV infection: an African perspective. 1910 17

Mechanisms responsible for HIV cardiomyopathy are unknown, but may include direct effects of HIV proteins on the heart. Transgenic mice (TG) expressing HIV Tat protein targeted to the myocardium, +/- Tat TG, have revealed anatomical and biochemical defects in the heart. The present studies were conducted to clarify the effect of Tat on cardiac function. In vivo hemodynamics was measured in awake mice after inserting a catheter tip in the left ventricle under general anesthesia. Under the age of 3 months, the heart rate (HR) was significantly lower in TG (591 +/- 47 vs. 716 +/- 45 bpm, TG versus FVB control (FVB), respectively (P < 0.05; n = 8-12). Other hemodynamic indexes, including left ventricular systolic pressure (LVSP), positive and negative dp/dt (mmHg/s), and left ventricular end diastolic pressure (LVEDP) remained indistinguishable from FVB. At 6 months, however, ventricular dysfunction was evident in TG (HR = 580 +/- 47 vs. 673 +/- 25 bpm, TG versus FVB, P < 0.05); LVSP (132 +/- 6 vs. 147 +/- 6 mmHg, TG versus FVB; P < 0.05); LVEDP (15 +/- 4 vs. 8 +/- 6 mmHg, TG vs. FVB, P < 0.05); +dp/dt = 8872 +/- 331 vs. 10026 +/- 796 mmHg/s TG versus FVB, P < 0.01) and -dp/dt (7403 +/- 432 vs. 8835 +/- 368 mmHg/s, TG versus FVB, P < 0.01; n = 8-12, in each group). The change in percentage of fractional shortening in response to isoproterenol was also significantly reduced in cardiac myocytes isolated from TG versus FVB (P < 0.05). Thus, targeted myocardial transgenic expression of HIV Tat in mice results in relative bradycardia, depression in systolic and diastolic functions in vivo, and blunted adrenergic responsiveness in vitro.
Cardiovasc Toxicol 2009 Mar
PMID:Dilated cardiomyopathy in transgenic mice expressing HIV Tat. 1933 63

HIV infection in patients is associated with a surprisingly high frequency of diastolic dysfunction followed by the development of a dilated cardiomyopathy. Potential mechanisms include direct effects of HIV proteins, including gp120. We have previously reported direct inotropic and p38 MAP kinase signaling effects of HIV gp120 on isolated cardiac myocytes in vitro. We now report effects of a single injection of HIV gp120 on cardiac hemodynamics in vivo. HIV gp120 (50 microg/kg) was injected intravenously and hemodynamics assessed at 1, 24, 48 and 72 h in freely ambulatory, awake rats. Rats injected with gp120 demonstrated a blunted diastolic response to increasing intravenous (IV) injections of the beta-adrenergic agonist, isoproterenol (ISO), compared with similarly instrumented controls at 48 h (gp120 vs. control, P < 0.01; n = 6, for each). Pre-treatment with the p38 MAP kinase inhibitor, SB 203580, prevented the diastolic dysfunction (gp120 + SB vs. control, P = NS; n = 6, for each). Hemodynamic changes correlated with inhibition of both p38 MAP kinase and troponin I phosphorylation by SB in vivo. There were no differences in ISO dose-response curves between gp120-treated and control rats at 1, 24 or 72 h (P = NS; n = 6, for each). Thus, evidence of diastolic dysfunction is apparent in vivo in rats following a single dose of HIV gp120. To our knowledge, this is the first report of a hemodynamic effect of an HIV protein in vivo. These findings lend further support to the hypothesis that the HIV virus, itself, may contribute to myocardial dysfunction in patients infected with HIV via a p38 MAP kinase mechanism.
Cardiovasc Toxicol 2009 Sep
PMID:p38 MAP kinase inhibitor prevents diastolic dysfunction in rats following HIV gp120 injection in vivo. 1964 60

To examine the effect of HIV infection on regional left ventricular dysfunction in cardiovascularly asymptomatic individuals. Nineteen HIV-negative and 27 HIV-positive cardiovascularly asymptomatic study participants in Baltimore, Maryland were selected and underwent tagged cardiac magnetic resonance imaging. Regional left ventricular myocardial mid-wall peak systolic circumferential strain (Ecc) and early diastolic strain rate (SRE) of the left ventricle were assessed with the use of the harmonic phase analysis. The average Ecc and SRE measurements were compared between HIV-negative and HIV-positive individuals. Compared with the HIV-negatives, the HIV-positives had lower average Ecc and SRE measurements in 90% of the 16 standard left ventricular segments. Of the 14 segments with decreased Ecc strain, 3 were statistically significant and of 14 with decreased strain rate (SRE), 6 were statistically significant. HIV infection may be associated with subclinical regional left ventricular systolic and diastolic dysfunction in individuals free of overt cardiovascular disease.
Int J Cardiovasc Imaging 2009 Dec
PMID:HIV infection and abnormal regional ventricular function. 1976 77

HIV/AIDS appears to increase the risk of both ischemic and hemorrhagic stroke. This increased risk is most apparent in the young HIV-infected population in which other risk factors for stroke are seldom evident. Mechanisms underlying the increased risk include opportunistic infectious meningitides and vasculitides, primary HIV vasculopathy, altered coagulation and cardioembolic events, although the cause may be multifactorial or remain cryptic. With better control of HIV via effective, highly active antiretroviral therapy, the role of many of these risks has been mitigated, only to be supplanted by an aging population with more conventional atherosclerotic risk factors magnified by the hyperlipidemia attending the use of protease inhibitors. Selecting the appropriate therapy for treating stroke in the HIV-infected patient is dependent on diagnostic rigor in identifying its underlying etiology.
Expert Rev Cardiovasc Ther 2009 Oct
PMID:Stroke in HIV infection and AIDS. 1981 69

Pulmonary vascular hypertension in general is a progressive, nearly always fatal condition that until recently has had very few treatment options. Our understanding of the pulmonary vascular disease process has opened the window to earlier screening techniques, diagnosis, and treatment options. However, all current treatment options are complex and expensive and therefore require clinical support strategies often necessitating specialized pulmonary hypertension treatment centers. Whether idiopathic or secondary, pulmonary arterial hypertension is characterized by the deregulated proliferation of pulmonary artery endothelial cells and intimal smooth muscle cells, both resistant to cellular apoptosis. Early recognition of such disregulation may lead to earlier diagnosis and treatment and thus alteration in the disease process. Screening of high-risk populations such as those with connective tissue disorders, HIV disease, congenital heart disease, portal hypertension, and those exposed to certain drugs and toxins such as methamphetamines and the diet drugs Dexfenfluramine and Fenfluramine is of utmost importance. Similarly, early symptom recognition in these high-risk groups is essential to earlier diagnosis and treatment.
Methodist Debakey Cardiovasc J 2009
PMID:The current treatment of pulmonary hypertension. 2007 61

Abacavir (ABC) is a guanosine nucleoside reverse transcriptase inhibitor (NRTI) with potent antiretroviral activity. Since NRTIs exhibit tissue-specific inhibition of mitochondrial DNA (mtDNA) synthesis, the ability of ABC to inhibit mtDNA synthesis in vivo was evaluated. Inbred wild-type (WT) and transgenic mice (TG) treated with ABC (3.125 mg/d p. o., 35 days) were used to define mitochondrial oxidative stress and cardiac function. Chosen TGs exhibited overexpression of HIV-1 viral proteins (NL4-3Deltagag/pol, non-replication competent), hemizygous depletion or overexpression of mitochondrial superoxide dismutase (SOD2(+/-) knock-out (KO) or MnSOD OX, respectively), overexpression of mitochondrially targeted catalase (MCAT), or double "knockout" deletion of aldehyde dehydrogenase activity (ALDH2 KO). Impact on mtDNA synthesis was assessed by comparing changes in mtDNA abundance between ABC-treated and vehicle-treated WTs and TGs. No changes in mtDNA abundance occurred from ABC treatment in any mice, suggesting no inhibition of mtDNA synthesis. Left ventricle (LV) mass and LV end-diastolic dimension (LVEDD) were defined echocardiographically and remained unchanged as well. These results indicate that treatment with ABC has no visible cardiotoxicity in these adult mice exposed for 5 weeks compared to findings with other antiretroviral NRTI studies and support some claims for its relative safety.
Cardiovasc Toxicol 2010 Jun
PMID:Absence of mitochondrial toxicity in hearts of transgenic mice treated with abacavir. 2037 2

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by elevation in pulmonary artery pressures causing progressive symptoms that lead to functional decline and poor quality of life. There are multiple causes of PAH including familial disease, connective tissue disease, and HIV. The estimated life expectancy is 4 years after onset of symptoms and approximately 6 to 7 years with PAH treatment. Much of the current research has focused on pharmacological treatments to improve functional status and decrease mortality. A comprehensive literature review was conducted using the CINAHL, PubMed, and MEDLINE to identify and synthesize current studies on human responses to PAH organized by emotional responses and physical functioning. Eight studies fulfilled the search criteria. Patients with PAH were learning to cope and live with uncertainty and treatment. Pulmonary arterial hypertension produced the emotional responses of anxiety, depression, and panic attacks along with impairments in cognition and memory as well as reductions in physical functioning.
J Cardiovasc Nurs
PMID:Human responses to pulmonary arterial hypertension: review of the literature. 2071 40


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