Article

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: 6.18). 09/2007; 120(2):150-7. DOI: 10.1016/j.ijcard.2006.11.143
Source: PubMed

ABSTRACT 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.

1 Bookmark
 · 
88 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the occurrence of ventricular systolic dysfunction in human immunodeficiency virus (HIV)-related pulmonary arterial hypertension (PAH). Patients with HIV-related PAH may develop ventricular systolic dysfunction both as a consequence of PAH progression or of the myocardial involvement from the HIV infection itself. Cardiac magnetic resonance imaging was applied to measure ejection fraction for the left ventricle and the right ventricle in patients with HIV-related PAH (n = 27) and in patients with PAH from other aetiologies (n = 115). In HIV-related PAH, ejection fraction values were lower and a higher proportion of patients presented with an advanced stage of ventricular dysfunction (55% vs. 25%; p = 0.009). In a multivariate model, PAH related to HIV infection remained independently associated with advanced ventricular dysfunction (p = 0.011). Patients with HIV-related PAH have more prevalent and severe ventricular systolic dysfunction compared to patients with PAH from other aetiologies.
    Heart & lung: the journal of critical care 03/2014; · 1.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: HIV-associated cardiomyopathy (HIVCM) is of clinical concern in developing countries because of a high HIV-1 prevalence, especially subtype C, and limited access to highly active antiretroviral therapy (HAART). For these reasons, we investigated the direct and indirect effects of HIV-1 subtype C infection of cultured human cardiomyocytes and the mechanisms leading to cardiomyocytes damage; as well as a way to mitigate the damage. We evaluated a novel approach to mitigate HIVCM using a previously reported gp120 binding and HIV-1 neutralizing aptamer called UCLA1. We established a cell-based model of HIVCM by infecting human cardiomyocytes with cell-free HIV-1 or co-culturing human cardiomyocytes with HIV-infected monocyte derived macrophages (MDM). We discovered that HIV-1 subtype C unproductively (i.e. its life cycle is arrested after reverse transcription) infects cardiomyocytes. Furthermore, we found that HIV-1 initiates apoptosis of cardiomyocytes through caspase-9 activation, preferentially via the intrinsic or mitochondrial initiated pathway. CXCR4 receptor-using viruses were stronger inducers of apoptosis than CCR5 utilizing variants. Importantly, we discovered that HIV-1 induced apoptosis of cardiomyocytes was mitigated by UCLA1. However, UCLA1 had no protective effective on cardiomyocytes when apoptosis was triggered by HIV-infected MDM. When HIV-1 was treated with UCLA1 prior to infection of MDM, it failed to induce apoptosis of cardiomyocytes. These data suggest that HIV-1 causes a mitochondrial initiated apoptotic cascade, which signal through caspase-9, whereas HIV-1 infected MDM causes apoptosis predominantly via the death-receptor pathway, mediated by caspase-8. Furthermore the data suggest that UCLA1 protects cardiomyocytes from caspase-mediated apoptosis, directly by binding to HIV-1 and indirectly by preventing infection of MDM.
    PLoS ONE 01/2014; 9(10):e110930. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Persons living with human immunodeficiency virus (HIV) are at increased risk of 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)-naïve PLWH at baseline and week 48 after initiation of ART. Results. Compared with age and gender-matched healthy controls, PLWH had a higher prevalence of DD (16.5% vs. 7.2%, P<.05) 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 and 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 while 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. Conclusion. The prevalence of echocardiographic abnormalities of ART-naïve PLWH was significantly higher than controls in this study. HIV infection was significantly with cardiac abnormalities. No significant change in echocardiographic abnormalities was observed after 48 weeks of ART and longer prospective studies are warranted.
    Clinical Infectious Diseases 02/2014; · 9.37 Impact Factor