What is it about?
By using a genetic rat model with HIV-1 expression, we found that chronic administration of a clinically used combination antiretroviral therapy regimen (cART) containing nucleoside reverse transcriptase inhibitors (Truvada) plus protease inhibitors (Reyataz+Norvir) resulted in enhanced circulating levels of cholesterol and triglyceride and increased plasma markers of oxidative and nitrosative stresses and systemic inflammation; significant cardiac dysfunction also occurred. In association, up-regulation of key lipogenic and nitric oxide mRNA genes and down-regulation of a master antioxidant transcription gene (Nrf2) were revealed. Importantly we discovered that dietary supplementation of Mg suppressed the expression of the lipogenic and nitrosative/oxidative genes and normalized the master antioxidant gene. In parallel, both blood cholesterol and triglyceride levels were lowered and the markers of oxidative/nitrosative stress and systemic inflammation were suppressed by Mg-supplementation. In a separate study, the impaired cardiac functions were mitigated by Mg supplementation.
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Why is it important?
Recent cART regimens have been highly effective in suppressing HIV replication and thus able to transition HIV infection from an acute disease to a chronic one. However, chronic HIV infection have resulted in higher risk of cardiovascular diseases ranging from myocardial infarction to heart failure which may in part caused by lipid metabolic disorder and chronic systemic inflammation associated with cART use. Our pre-clinical study strongly suggests that dietary Mg-supplementation alone can suppress abnormal metabolic and oxidative/inflammatory side effects caused by chronic cART administration in HIV patients, and thus protect against the impaired cardiac function.
Perspectives
Cardiovascular disease (CVD) is one of the leading causes of increased mortality in people living with HIV and receiving cART. Searching for effective therapeutic strategies in curbing HIV-associated CVDs remains challenging. Since Mg is relative safe and inexpensive, our study suggests that oral Mg supplementation may be used as an effective adjunct therapy to alleviate HIV- and cART-induced lipid metabolic disorder and oxidative/nitrosative stresses leading to CVD in people living with HIV.
I. Tong Mak
George Washington University
Read the Original
This page is a summary of: Mg-supplementation attenuated lipogenic and oxidative/nitrosative gene expression caused by Combination Antiretroviral Therapy (cART) in HIV-1-transgenic rats, PLoS ONE, January 2019, PLOS,
DOI: 10.1371/journal.pone.0210107.
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