Atorvastatin suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells

AbstractHyperhomocysteinemia is regarded as an independent risk factor for vascular diseases, and homocysteine is supposed to contribute to oxidative stress and endothelial damage. Statin therapy is an established intervention to reduce the risk of acute events in patients suffering from cardiovascular diseases. Apart from their lipid-lowering capacity, statins also exert anti-inflammatory and antioxidant effects. As cellular immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular diseases, the anti-inflammatory capacity of statins could partly be responsible for the beneficial effects observed in patients. Earlier we reported that stimulated peripheral blood mononuclear cells (PBMCs) release homocysteine. Here we studied the influence of atorvastatin on homocysteine production in stimulated PBMCs and compared changes in cysteine concentrations and in neopterin production, which is a sensitive indicator of cellular immune activation. Stimulation of human PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significant homocysteine and neopterin production compared to unstimulated cells, whereas cysteine concentrations remained unchanged. Treatment of PBMCs with increasing doses of atorvastatin (10–100μM) suppressed both biochemical pathways in a dose-dependent manner, and cell proliferation was inhibited in parallel. Again, cysteine levels were not influenced by any treatment. The down-regulating effect of atorvastatin on homocysteine formation in vitro indicates that statins may prevent homocysteine accumulation in the blood via immunosuppression.

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Peripheral Blood Mononuclear Cells and Platelets Mitochondrial Dysfunction, Oxidative Stress, and Circulating mtDNA in Cardiovascular Diseases

Journal of Clinical Medicine ◽

10.3390/jcm9020311 ◽

2020 ◽

Vol 9 (2) ◽

pp. 311 ◽

Cited By ~ 4

Author(s):

Abrar Alfatni ◽

Marianne Riou ◽

Anne-Laure Charles ◽

Alain Meyer ◽

Cindy Barnig ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiovascular Diseases ◽

Mitochondrial Dysfunction ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Oxidative Capacity ◽

Ros Production ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

Cardiovascular diseases (CVDs) are devastating disorders and the leading cause of mortality worldwide. The pathophysiology of cardiovascular diseases is complex and multifactorial and, in the past years, mitochondrial dysfunction and excessive production of reactive oxygen species (ROS) have gained growing attention. Indeed, CVDs can be considered as a systemic alteration, and understanding the eventual implication of circulating blood cells peripheral blood mononuclear cells (PBMCs) and or platelets, and particularly their mitochondrial function, ROS production, and mitochondrial DNA (mtDNA) releases in patients with cardiac impairments, appears worthwhile. Interestingly, reports consistently demonstrate a reduced mitochondrial respiratory chain oxidative capacity related to the degree of CVD severity and to an increased ROS production by PBMCs. Further, circulating mtDNA level was generally modified in such patients. These data are critical steps in term of cardiac disease comprehension and further studies are warranted to challenge the possible adjunct of PBMCs’ and platelets’ mitochondrial dysfunction, oxidative stress, and circulating mtDNA as biomarkers of CVD diagnosis and prognosis. This new approach might also allow further interesting therapeutic developments.

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Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2005.189 ◽

2005 ◽

Vol 43 (10) ◽

Cited By ~ 8

Author(s):

Katharina Schroecksnadel ◽

Christiana Winkler ◽

Barbara Wirleitner ◽

Harald Schennach ◽

Günter Weiss ◽

...

Keyword(s):

Salicylic Acid ◽

Peripheral Blood Mononuclear Cells ◽

Immune Activation ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Anti Inflammatory

AbstractInflammation, immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular disorders. In addition to markers of inflammation, moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease, and there is a link between the activation of immunocompetent cells and the enhanced formation of homocysteine in vitro. Likewise, anti-inflammatory drugs and nutrients rich in antioxidant vitamins are able to reduce cardiovascular risk and to slow down the atherogenic process. Resveratrol, a phenolic antioxidant synthesized in grapes and vegetables and present in wine, has also been supposed to be beneficial for the prevention of cardiovascular events. Apart from its strong antioxidant properties, resveratrol has also been demonstrated to act as an anti-inflammatory agent. In this study the influence of resveratrol on the production of homocysteine by stimulated human peripheral blood mononuclear cells (PBMCs) was investigated. Results were compared to earlier described effects of the anti-inflammatory compounds aspirin and salicylic acid and of the lipid-lowering drug atorvastatin. Stimulation of PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significantly higher homocysteine accumulation in supernatants compared with unstimulated cells. Treatment with 10–100μM resveratrol suppressed homocysteine formation in a dose-dependent manner. Resveratrol did not influence the release of homocysteine from resting PBMCs. The data suggest that resveratrol may prevent homocysteine accumulation in the blood by suppressing immune activation cascades and the proliferation of mitogen-driven T-cells. The effect of resveratrol to down-regulate the release of homo-cysteine was comparable to the decline of neopterin concentrations in the same experiments. The suppressive effect of resveratrol was very similar to results obtained earlier with aspirin, salicylic acid and atorvastatin; however, it appeared that doses of compounds needed to reduce homocysteine levels to 50% of stimulated cells were always slightly lower than those necessary to achieve the same effect on neopterin concentrations. The influence of resveratrol and of all the other compounds on homocysteine production appears to be independent of any direct effect on homocysteine biochemistry.

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