Cytokines in HIV-associated cardiomyopathy

AP-HP, Hôpital Paul Brousse, Department of Internal Medicine and Infectious Diseases, Université Paris-Sud 11, Faculté de Médecine, de Bicêtre, France 94804 Villejuif, France.
International journal of cardiology (Impact Factor: 4.04). 09/2007; 120(2):150-7. DOI: 10.1016/j.ijcard.2006.11.143
Source: PubMed


Among the multiple cardiac manifestations occurring in HIV-infected patients, cardiomyopathy is one of the most challenging. Its incidence has only slightly decreased since the introduction of highly active antiretroviral therapy (HAART). Also, its pathogenesis remains relatively unclear. Although several studies demonstrated the presence of HIV genome in the heart of patients, more recent developments found that viral infection plays an indirect role only, as well as they recognized the contribution of proinflammatory cytokines in the progression of the disease. Experimental studies on animals and cultured myocytes have established the signalling pathway triggered by proinflammatory cytokines in heart failure and cardiomyopathy. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and IL-6 promote expression of inducible nitric oxide synthase (iNOS) in cardiomyocytes through activation of p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappaB (NFkappaB). TNF-alpha and high concentrations of NO also induce cardiomyocyte apoptosis by TNF type 1 receptor activation. This biological framework, which is also involved in progression of cardiomyopathy in humans, is more pronounced in HIV-infected patients, in whom proinflammatory cytokines TNF-alpha, IL-1 and IL-6 are increased, resulting in an enhanced expression of cardiac iNOS, especially in patients with a low CD4 T cell count. This may account for the worse outcome of heart failure in HIV-infected patients. However, there are only few data today to support future therapeutic implications of cytokines antagonism in treatment of HIV-infected patients with cardiomyopathy. Whether modulation of TNF production or selective inhibition of p38 MAPK pathway could be useful approaches remains uncertain.

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    • "PLWH have high level of inflammation biomarkers, which may predispose them to cardiac dysfunction[28]. Monsuez et al[29]reported cardiac involvement with cardiomyocyte apoptosis in HIV infection primarily due to proinflammatory cytokines. Third, several studies suggest that cardiac dysfunction in PLWH is associated with ART[30,31]. "
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    ABSTRACT: Background: Persons living with human immunodeficiency virus (HIV) are at increased risk of developing cardiovascular disease. Few studies have focused on echocardiographic abnormalities in this population. Methods: China AIDS Clinical Trial 0810 is a prospective, multicenter cohort study of persons living with HIV (PLWH). We performed an echocardiography substudy of 325 PLWH. We examined the prevalence of left ventricular systolic dysfunction (LVSD), diastolic dysfunction (DD), pulmonary arterial hypertension (PAH), and increased left ventricular mass (ILVM) in antiretroviral therapy (ART)-naive PLWH at baseline and week 48 after initiation of ART. Results: Compared with age- and sex-matched healthy controls, PLWH had a higher prevalence of DD (16.5% vs 7.2%, P < .027) and a marginally significant higher prevalence of LVSD (7.3% vs 2.1%, P = .056). The increase in the prevalence of DD from baseline to week 48 in PLWH was marginally significant (P = .056). No significant difference was observed in the prevalence of LVSD, PAH, or ILVM at baseline and week 48 in PLWH. In logistic regression analysis of all participants, age was significantly associated with LVSD; HIV infection, age, and hypertension were associated with DD whereas HIV infection and hypertension were associated with ILVM at baseline. Logistic regression analysis of PLWH showed that only age was significantly associated with LVSD and DD. Conclusions: The prevalence of echocardiographic abnormalities was significantly higher in ART-naive PLWH than in controls. HIV infection was significantly associated with cardiac abnormalities. No significant change in echocardiographic abnormalities was observed after 48 weeks of ART. Longer-term prospective studies are warranted.
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    • "This high concentration of nitric oxide (NO) and TNF-alpha induces cardiomyocyte apoptosis by TNF type 1 receptor activation. This effect is more pronounced in HIV infected individuals, especially in patients with low CD4 count, which accounts for the worse outcomes of heart failure in HIV patients (Monsuez et al., 2007). Severity of the disease ranges from incidental microscopic findings on autopsy to clinically significant heart disease causing severe cardiac dysfunction (Sani, 2008). "
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    ABSTRACT: HIV infection is a leading health problem across the entire world, including United States. Recent advances in medicine have led to a significant decline in mortality associated with HIV infection and hence increased life expectancy in HIV-infected individuals. Cardiovascular complications represent an increasingly important health concern in HIV-infected population especially after theintroduction of anti-retroviral therapy. Numerous researchstudies have demonstrated the increased prevalence of cardiovascular disease in HIV infected individuals. The etiology of the preponderance of cardiovascular manifestations associated with HIV is still not well established. It may be attributed to virus itself, the effects of anti-retroviral medications; or altered immune mechanismsassociated with the infection. The stratification of cardiovascular risk and cardiovascular monitoring in HIV patients poses a challenge to the physicians in the modern age. The cardiovascular lesions reported in HIV infection include pericardial disease with effusion and tamponade, myocarditis, dilated cardiomyopathy with left ventricular dysfunction, endocarditis, coronary artery disease,pulmonary hypertension, cardiac autonomic dysfunction and certain rare neoplasms. HIV infection in itself can be a potential risk factor for accelerated coronary artery disease. The advent of anti-retroviral therapy has witnessed an increased risk of metabolic syndrome, hyperlipidemia and insulin resistance in HIV patients onHAART. Thorough understanding of the course of cardiac related illnesses in HIV infection helps in early diagnosis, appropriate intervention and therapy. The following review overviews the cardiac abnormalities associated with HIV infection focusing on early diagnosis, therapy and prognosis.
    Full-text · Article · Jan 2009 · Journal of Antivirals and Antiretrovirals
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    ABSTRACT: As the number of children infected with HIV rises so does the number of patients with cardiac complications. These complications are miscellenous with uncharacteristic symptoms. Children with congestive cardiomiopathy resulting from HIV infection may manifest symptoms and signs of cardiac failure but most frequently the clinical course mimics infection of the respiratory system. All HIV positive children with symptoms suggesting respiratory tract infection must be evaluated cardiologically. In this paper we present an HIV infected 2,5 year old boy with congestive cardiomiopathy.
    No preview · Article · Nov 2007 · Pediatria polska
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