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
 · 
74 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
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of macrophage activation, traffic, and accumulation on cardiac pathology was examined in twenty-three animals. Seventeen animals were SIV-infected, 12 were CD8-lymphocyte depleted, and the remaining 6 were uninfected controls (2 CD8-lymphocyte depleted, 4 non-depleted). None of the uninfected controls had cardiac pathology. One of five (20%) SIV-infected, non-CD8 lymphocyte depleted animals had minor cardiac pathology with increased numbers of macrophages in ventricular tissue compared to controls. Seven of the twelve (58%) SIV-infected, CD8-lymphocyte depleted animals had cardiac pathology in ventricular tissues, including macrophage infiltration and myocardial degeneration. The extent of fibrosis (measured as the percentage of collagen per tissue area), was increased 41% in SIV-infected, CD8-lymphocyte depleted animals with cardiac pathology compared to animals without pathological abnormalities. The number of CD163+ macrophage increased significantly in SIV-infected, CD8-lymphocyte depleted animals with cardiac pathology compared to ones without pathology (1.66 fold) and controls (5.42 fold). The percent of collagen (percentage of collagen per total tissue area) positively correlated with macrophage numbers in ventricular tissue in SIV-infected animals. There was an increase of BrdU+ monocytes in the heart during late SIV infection, regardless of pathology. These data implicate monocyte/macrophage activation and accumulation in the development of cardiac pathology with SIV infection.
    AIDS research and human retroviruses 02/2014; · 2.18 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