HIV infection is an independent risk factor for atherosclerosis development and cardiovascular damage. As vessel wall mesenchymal stem cells (MSCs) are involved in the regulation of vessel structure homeostasis, we investigated the role of Tat, a key factor in HIV replication and pathogenesis, in MSC survival and differentiation. The survival of subconfluent MSCs was impaired when Tat was added at high concentrations (200-1,000 ng/ml), whereas lower Tat concentrations (1-100 ng/ml) did not promote apoptosis. Tat enhanced the differentiation of MSC toward adipogenesis by the transcription and activity upregulation of PPARγ. This Tat-related modulation of adipogenesis was tackled by treatment with antagonists of Tat-specific receptors such as SU5416 and RGD Fc. In contrast, Tat inhibited the differentiation of MSCs to endothelial cells by downregulating the expression of VEGF-induced endothelial markers such as Flt-1, KDR, and vWF. The treatment of MSCs with Tat-derived peptides corresponding to the cysteine-rich, basic, and RGD domains indicated that these Tat regions are involved in the inhibition of endothelial marker expression. The Tat-related impairment of MSC survival and differentiation might play an important role in vessel damage and formation of the atherosclerotic lesions observed in HIV-infected patients.
"HIV-specific mechanisms include immune dysfunction and increased inflammatory response leading to increased thrombosis and changes in lipid levels and cholesterol metabolism, which are also responsible for MetS and cardiovascular risk in the general population. Tat, a key molecule in HIV replication and pathogenesis can affect both mesenchymal stem cells survival and differentiation by downregulating the expression of VEGF-induced endothelial markers and this might play an instrumental role in vessel damage and in the atherosclerotic lesions observed in HIV infection . "
[Show abstract][Hide abstract] ABSTRACT: The success of highly active antiretroviral therapy (HAART) has determined a dramatic decline in AIDS- and immunodeficiency-related causes of death in the HIV-infected population. As life-expectancy increases, such individuals have become gradually exposed not only to the effects of aging itself, but also to the influence of environmental risk factors, which are known to act in the general population. These features can lead to obesity, diabetes mellitus and ultimately cardiovascular diseases (CVD). Metabolic complications and abnormal fat distribution were frequently observed after a few years of antiretroviral therapy and, as the array of antiretroviral drugs became broader, long term metabolic alterations are becoming far more common worldwide. Nevertheless, the risk of not being on HAART is overwhelmingly greater than the metabolic adverse events in terms of morbidity and mortality events. HIV/HAART-induced metabolic unbalances overlap in some extent the components of Metabolic Syndrome (MetS) and its high rates in the HIV population place infected individuals in an elevated CVD risk category. MetS can explain at least in part the emergence of CVD as the major morbidity and mortality conditions in the HIV population. In this review we convey information on the underlying aspects of MetS during HIV infection, highlighting some physiopathological and epidemiological features of this comorbidity along with the role played by HIV itself and the synergy action of some antiretroviral drugs. Considerations on MetS management in the HIV population are also depicted.
AIDS Research and Therapy 12/2013; 10(1):32. DOI:10.1186/1742-6405-10-32 · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HIV-infected patients have a significantly higher risk of developing cardiovascular events during the progression of HIV disease. Atherosclerosis, myocardial infarction, cerebrovascular injury, pulmonary hypertension and thrombosis are consistently described in both combined antiretroviral therapy (cART)-treated and naive HIV-positive patients as major clinical complications. Recent studies indicate that the pathogenesis of cardiovascular lesions in HIV-positive patients is related to direct and indirect effects of HIV infection on vessel structures, independently of traditional risk factors. HIV infection strongly interferes with the biology of several cellular targets such as macrophage and endothelial cells. Moreover, HIV induces a profound derangement of lipid metabolism and inflammatory cytokine networks that are directly involved in atherogenesis and progressive impairment of the cardiovascular system.In this review, we discuss these major HIV-related mechanisms able to promote atherosclerosis and cardiovascular diseases in HIV-positive patients.
Journal of Cardiovascular Medicine 05/2013; 14(11). DOI:10.2459/JCM.0b013e3283619331 · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Anaemia and thrombocytopenia are haematological disorders that can be detected in many human immunodeficiency virus (HIV)-positive patients during the development of HIV infection. The progressive decline of erythrocytes and platelets plays an important role both in HIV disease progression and in the clinical and therapeutic management of HIV-positive patients. HIV-dependent impairment of the megakaryocyte and erythrocyte lineages is multifactorial and particularly affects survival, proliferation and differentiation of bone marrow (BM) CD34+ haematopoietic progenitor cells, the activity of BM stromal cells and the regulation of cytokine networks. In this review, we analyse the major HIV-related mechanisms that are involved in the genesis and development of the anaemia and thrombocytopenia observed in HIV positive patients.
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