Possible Biomarkers for the Early Detection of HIV-associated Heart Diseases: A Proteomics and Bioinformatics Prediction.
The frequency of cardiovascular disorders is increasing in HIV-infected individuals despite a significant reduction in the viral load by antiretroviral therapies (ART). Since the CD4 + T-cells are responsible for the viral load as well as immunological responses, we hypothesized that chronic HIV-infection of T-cells produces novel proteins/enzymes that cause cardiac dysfunctions. To identify specific factors that might cause cardiac disorders without the influence of numerous cofactors produced by other pathogenic microorganisms that co-inhabit most HIV-infected individuals, we analyzed genome-wide proteomes of a CD4 + T-cell line at different stages of HIV replication and cell growth over > 6 months. Subtractive analyses of several hundred differentially regulated proteins from HIV-infected and uninfected counterpart cells and comparisons with proteins expressed from the same cells after treating with the antiviral drug Zidovudine/AZT and inhibiting virus replication, identified a well-coordinated network of 12 soluble/diffusible proteins in HIV-infected cells. Functional categorization, bioinformatics and statistical analyses of each protein predicted that the expression of cardiac-specific Ca2 + kinase together with multiple Ca2 + release channels causes a sustained overload of Ca2 + in the heart which induces fetal/cardiac myosin heavy chains (MYH6 and MYH7) and a myosin light-chain kinase. Each of these proteins has been shown to cause cardiac stress, arrhythmia, hypertrophic signaling, cardiomyopathy and heart failure (p = 8 × 10(- 11)). Translational studies using the newly discovered proteins produced by HIV infection alone would provide additional biomarkers that could be added to the conventional markers for an early diagnosis and/or development of specific therapeutic interventions for heart diseases in HIV-infected individuals.
Laboratory of Viral Oncology and Proteomics Research, Keck School of Medicine, University of Southern California, Cancer Research Laboratory Building, 1303 North Mission Rd, Los Angeles, CA 90033, USA.
Suraiya
S
Rasheed
Laboratory of Viral Oncology and Proteomics Research, Keck School of Medicine, University of Southern California, Cancer Research Laboratory Building, 1303 North Mission Rd, Los Angeles, CA 90033, USA.
Rahim
R
Hashim
Laboratory of Viral Oncology and Proteomics Research, Keck School of Medicine, University of Southern California, Cancer Research Laboratory Building, 1303 North Mission Rd, Los Angeles, CA 90033, USA.
Jasper S
JS
Yan
Fetal-cardiac myosin; HIV-cardiomyopathy; ITPR; Myosin light-chain kinase; PI3K; Ryanodine-receptors