Hypercholesterolemia increases myocardial oxidative and nitrosative stress thereby leading to cardiac dysfunction in apoB-100 transgenic mice

Csont, Tamás; Bereczki, Erika; Bencsik, Péter; Fodor, Gabriella; Görbe, Anikó; Zvara, Ágnes; Csonka, Csaba; Puskás, László G.; Sántha, Miklós

doi:10.1016/j.cardiores.2007.06.006

Cited by 101 publications

(118 citation statements)

References 42 publications

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“…In a clinical report, Meng et al (36) described that use of HIV protease inhibitors, including RTV, in 98 HIV patients was associated with left ventricular morphological changes and diastolic dysfunction. Two experimental reports demonstrated that hyperlipidemia can exert direct oxidative and nitrosative stress on myocardium, leading to cardiac dysfunction in rats (38) and mice (12). In the current study, substantial hyperlipidemia occurred early (by 1-2 wk), but significant decreases in LV systolic and diastolic function were revealed only at or after 5 wk of RTV treatment, and the progression of dysfunction appeared to coincide with the appearance of WBC infiltration.…”

Section: Discussionsupporting

confidence: 55%

Mg supplementation attenuates ritonavir-induced hyperlipidemia, oxidative stress, and cardiac dysfunction in rats

Mak

Kramer

Chen

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Mak IT, Kramer JH, Chen X, Chmielinska JJ, Spurney CF, Weglicki WB. Mg supplementation attenuates ritonavir-induced hyperlipidemia, oxidative stress, and cardiac dysfunction in rats. Am J Physiol Regul Integr Comp Physiol 305: R1102-R1111, 2013. First published September 18, 2013 doi:10.1152/ajpregu.00268.2013.-Use of protease inhibitors (PI) in HIV patients is associated with hyperlipidemia and increased risk of coronary heart disease. Chronic systemic and cardiac effects of ritonavir (RTV), a universal PI booster, and Mg supplementation were examined. RTV was administered (75 mg·kg Ϫ1 ·day Ϫ1 po) to LewisϫBrown-Norway hybrid (LBNF1) rats for up to 8 wk; significant increases in plasma triglyceride and cholesterol occurred from 8 days to 8 wk. At 5 wk, the expression of selected hepatic genes (CYP7A1, CITED2, G6PC, and ME-1), which are key to lipid catabolism/synthesis, were altered toward lipogenesis. Dietary Mg supplementation (six-fold higher) completely reversed the altered expression of these genes and attenuated both hypertriglyceridemia and hypercholesterolemia. Neutrophils isolated from the RTV-treated rats displayed a three-fold higher basal and a twofold higher stimulated superoxide production; plasma isoprostane and red blood cell (RBC) GSSG levels were elevated twoto three-fold. All oxidative indices were normalized by Mg supplementation. After 5 wk, RTV caused significant decreases in cardiac left ventricular (LV) shortening fraction and LV ejection fraction; mitral valve early/late atrial ventricular filling (E/A) ratio was reduced accompanied by LV posterior wall thinning. Immunohistochemical staining revealed significant white blood cell (WBC) infiltration (5 wk) and prominent fibrosis (8 wk) in the RTV hearts. Mg supplementation attenuated RTV-induced declines in systolic and diastolic (improved mitral valve E/A ratio) function (Ͼ70%), lessened LV posterior wall thinning (by 75%), and substantially decreased the pathological markers. The known clinical hyperlipidemia effects of RTV can be mimicked in the LBNF1 rats; in association, systemic oxidative stress and progressive cardiac dysfunction occurred. Remarkably, Mg supplementation alone suppressed RTV-mediated hyperlipidemia, oxidative stress, and cardiac dysfunction.HIV-1 protease inhibitor ritonavir; hepatic metabolic gene regulation; hyperlipidemia; oxidative stress; cardiac dysfunction; dietary Mg supplementation ACCORDING TO A RECENT REPORT (47), there are 34 million people worldwide infected with HIV-1, and of these, 1.3 million are in the United States (7). Nucleoside/nucleotide analogs, with Zidovudine (AZT) as the prototype compound, were first introduced in the late 1980s and continue to play a significant role in HIV therapy (13). With the introduction of protein inhibitors (PIs) in the mid 1990s, HIV-1 replication in the patients was shown to be dramatically reduced, and currently, to the extent that HIV-1 infection has become a more manageable disease (20,23). However, along with the chronic use of PIs, significant metabolic si...

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Section: Discussionsupporting

confidence: 55%

Mg supplementation attenuates ritonavir-induced hyperlipidemia, oxidative stress, and cardiac dysfunction in rats

Mak

Kramer

Chen

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…We have previously shown in rats and in apoB-100 transgenic mice that hypercholesterolemia increases nitro-oxidative stress, which leads to myocardial functional deterioration [26,27]. Here, we have also examined the correlation pattern of serum lipids with nitrotyrosine in CAD patients and shown that nitrotyrosine correlated positively with triglyceride, total-and LDL cholesterol levels, and negatively with HDL cholesterol.…”

Section: Serum Lipids Correlate With Nitrotyrosine and Mmps Activitymentioning

confidence: 98%

Serum lipids and cardiac function correlate with nitrotyrosine and MMP activity in coronary artery disease patients

Bencsik

Sasi

Kiss

et al. 2015

Eur J Clin Investigation

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“…We have previously shown in rats and in apoB-100 transgenic mice that hypercholesterolemia increases nitro-oxidative stress, which leads to myocardial functional deterioration [73,74]. Here, we have also examined the correlation pattern of serum lipids with nitrotyrosine in patients with CAD and shown that nitrotyrosine correlated positively with triglyceride, total and LDL cholesterol levels, and negatively with HDL cholesterol.…”

Section: Serum Lipids Correlate With Nitrotyrosine and Mmps Activitymentioning

confidence: 80%

Peroxynitrite - matrix metalloproteinase and erythropoietin receptor signaling pathways in ischemic heart disease

Kiss

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Hypercholesterolemia increases myocardial oxidative and nitrosative stress thereby leading to cardiac dysfunction in apoB-100 transgenic mice

Abstract: We conclude that hypercholesterolemia but not hypertriglyceridemia leads to increased formation of superoxide and peroxynitrite, and thereby results in cardiac dysfunction in hearts of human apoB100 transgenic mice.

Cited by 101 publications

References 42 publications

Mg supplementation attenuates ritonavir-induced hyperlipidemia, oxidative stress, and cardiac dysfunction in rats

Mg supplementation attenuates ritonavir-induced hyperlipidemia, oxidative stress, and cardiac dysfunction in rats

Serum lipids and cardiac function correlate with nitrotyrosine and MMP activity in coronary artery disease patients

Peroxynitrite - matrix metalloproteinase and erythropoietin receptor signaling pathways in ischemic heart disease

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