Investigation of heart lipid changes in acute β-AR activation-induced sudden cardiac death by time-of-flight secondary ion mass spectrometry

ToF-SIMS, PCA and PLS-DA were combined to compare lipid profiles of myocardial tissue in sudden cardiac death and normal, mice and humans. SIMS imaging was utilized to correlate the composition and structural changes.

Correction: Investigation of heart lipid changes in acute β-AR activation-induced sudden cardiac death by time-of-flight secondary ion mass spectrometry

Correction for ‘Investigation of heart lipid changes in acute β-AR activation-induced sudden cardiac death by time-of-flight secondary ion mass spectrometry’ by Jia-Qian Lou, et al., Analyst, 2020, DOI: 10.1039/d0an00768d.

Exercise Training under Exposure to Low Levels of Fine Particulate Matter: Effects on Heart Oxidative Stress and Extra-to-Intracellular HSP70 Ratio

Fine particulate matter (PM2.5) promotes heart oxidative stress (OS) and evokes anti-inflammatory responses observed by increased intracellular 70 kDa heat shock proteins (iHSP70). Furthermore, PM2.5 increases the levels of these proteins in extracellular fluids (eHSP70), which have proinflammatory roles. We investigated whether moderate and high intensity training under exposure to low levels of PM2.5 modifies heart OS and the eHSP70 to iHSP70 ratio (H-index), a biomarker of inflammatory status. Male mice (n=32), 30 days old, were divided into six groups for 12 weeks: control (CON), moderate (MIT) and high intensity training (HIT), exposure to 5 μg of PM2.5 daily (PM2.5), and moderate and high intensity training exposed to PM2.5 (MIT + PM2.5 and HIT + PM2.5 groups). The CON and PM2.5 groups remained sedentary. The MIT + PM2.5 group showed higher heart lipid peroxidation levels than the MIT and PM2.5 groups. HIT and HIT + PM2.5 showed higher heart lipid peroxidation levels and lower eHSP70 and H-index levels compared to sedentary animals. No alterations were found in heart antioxidant enzyme activity or iHSP70 levels. Moderate exercise training under exposure to low levels of PM2.5 induces heart OS but does not modify eHSP70 to iHSP70 ratio (H-index). High intensity exercise training promotes anti-inflammatory profile despite exposure to low levels of PM2.5.

Effect of valsartan on cardiac senescence and apoptosis in a rat model of cardiotoxicity

The clinical application of doxorubicin is limited by its cardiotoxicity. The present study investigated the effect of valsartan on doxorubicin-induced cardiotoxicity in rats. Rats were divided into 6 groups: control, control + valsartan (10 mg/kg, for 14 days, orally), doxorubicin-treated (2.5 mg/kg, 3 times/week for 2 weeks, intraperitoneally), valsartan then doxorubicin, valsartan + doxorubicin, and doxorubicin then valsartan. ECG, isolated heart, lipid peroxidation (thiobaribituric acid reactive substances (TBARS)), total antioxidant capacity (TAC), and Bax, Bcl-2, and senescence marker protein 30 (SMP30) gene expression were measured in cardiac tissue. Blood samples were collected to measure lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB). Doxorubicin significantly increased LDH, CK-MB, TBARS, heart rate (HR), Bax gene expression, and −dP/dtmax and decreased TAC, Bcl-2 and SMP30 gene expression, left ventricular developed pressure (LVDP), and +dP/dtmax. Also, doxorubicin lengthened ST, QT, and QTc intervals. Concurrent or post- but not pre-treatment of doxorubicin-treated rats with valsartan reduced LDH, CK-MB, TBARS, HR, Bax gene expression, −dP/dtmax, and ST, QT, and QTc intervals and increased TAC, Bcl-2 and SMP30 gene expression, LVDP, and +dP/dtmax. Therefore, we conclude that concurrent or post- but not pre-treatment of doxorubicin-induced rats with valsartan attenuated doxorubicin-induced cardiotoxicity through inhibiting oxidative stress, apoptosis, and senescence.

Abstract 19022: Endothelial Cell Specific CD36 Deletion Reduces Uptake of Fatty Acids by the Heart

Circulating fatty acids must cross the endothelial cell (EC) barrier to supply cardiomyocytes (CM). How this occurs is unknown. Cluster of differentiation (CD) 36 is a membrane associated protein whose total body deletion leads to reduced uptake of non-esterified fatty acids by heart, skeletal muscle and adipose tissue. To determine the contribution of EC versus CM CD36 in heart lipid uptake, we floxed CD36 and created EC- and CM-specific knockout (KO) mice. CD36 mRNA was reduced >50% in the heart, lung and skeletal muscle of EC-CD36 KO mice; CM-CD36 KO mice also had an ~50% reduction of CD36 mRNA levels in the heart. Both CM- and EC-specific CD36 ablation altered heart mRNA levels of glucose transport and oxidation genes (e.g. Glut1 ~2-fold increased, PDK4 ~0.5-fold decreased); these changes were similar to those found in mice with total body CD36 deletion. Loss of EC-CD36 led to increased plasma free fatty acid levels and prevented heart lipid droplet accumulation after an overnight fast (assessed by EM and oil red O staining). Lipid droplet accumulation was less affected in CM-CD36 KO hearts. To quantify the role of CD36 in the uptake of short chain vs. long chain fatty acids we simultaneously injected mice with radiolabeled [14C]hexanoic acid and [3H]oleic acid. Compared to both floxed-CD36 and CM-CD36 KO mice, plasma clearance of oleic acid was significantly delayed, and heart and quadriceps muscle uptake of oleic acid was reduced >50% in EC-CD36 KO and total-CD36 KO mice. Hexanoic acid uptake was not decreased by either deletion. Therefore, CD36 in EC is needed for the accumulation of long chain fatty acids in the heart and appears to be required for movement of fatty acids across the EC barrier.

Different Effects of Resveratrol on Dose-Related Doxorubicin-Induced Heart and Liver Toxicity

The aim of the study was to evaluate the effect of resveratrol in doxorubicin-induced cardiac and hepatic toxicity. Doxorubicin was administered once a week throughout the period of 7 weeks with 1.0 or 2.0 mg/kg body weight or concomitantly with resveratrol (20 mg/kg of feed). Heart and liver toxicity was histologically and biochemically evaluated. Resveratrol protected from the heart lipid peroxidation caused by 1 mg doxorubicin and it sharply diminished superoxide dismutase activity. An insignificant effect of resveratrol on the lipid peroxidation level and the superoxide dismutase activity was observed in the hearts of rats administered a higher dose of doxorubicin. However, resveratrol attenuate necrosis and other cardiac histopathological changes were induced by a high dose of doxorubicin. Interestingly, it slightly intensified adverse cardiac histological changes in rats receiving a lower dose of doxorubicin. Resveratrol did not have any protective effect on the hepatic oxidative stress, while exerting a mild beneficial effect on the morphological changes caused by doxorubicin. All in all, this study has shown different effects of resveratrol on dose-related doxorubicin-induced heart and liver toxicity. Resveratrol may modulate the hepatic and cardiac effect of doxorubicin, depending on the drug dose.