Background: Hypercholesterolemia is a major risk factor for cardiovascular disease. It has been reported that pineapple contains healthy nutrients and phytochemicals associated with antioxidant and anti-inflammatory capacities. No investigation exists concerning the effect of pineapple consumption modulating hypercholesterolemia-induced cardiac damage in high-cholesterol diet (HCD)-fed rats. This study evaluated the effect of pineapple consumption on lipid-lowering, cardiac oxidative stress and inflammation in HCD-fed rats. Methods: Male Sprague–Dawley rats were fed with HCD, in the presence and absence of Pineapple (Ananas comosus L.) cv. Pattavia powder for 8 weeks. Then, serum lipid profiles, liver and renal function tests, cardiac oxidative stress and pro-inflammatory cytokines were determined. Results: Daily pineapple consumption reduced weight gain, serum lipid profiles, atherogenic coefficient (AC), cardiac risk ratio (CRR), and liver enzyme activity, without causing renal dysfunction. Pineapple consumption also restores cardiac protein carbonyl (cPC) content, reduces cardiac malondialdehyde (MDA), cardiac pro-inflammation cytokine IL-6 and IL-1β levels. Conclusion: Pineapple possesses antioxidant and lipid-lowering properties and daily consumption alleviates hypercholesterolemia-induced cardiac lipid peroxidation and pro-inflammation elevation in an in vivo model. This study demonstrates that pineapple is a potential candidate for cardioprotection against hypercholesterolemia.

Vascular endothelial cell (EC)-derived factors play an important role in endothelial–cardiomyocyte crosstalk and could save cardiomyocytes (CMs) from injury. The manipulation of endothelial cells to secrete protective factors could enhance cardioprotection. Secretory leukocyte protease inhibitor (SLPI) has been known to protect the heart. The goal of this study was to evaluate the in vitro paracrine protective effect and mechanisms of EC-derived human SLPI on cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury. Stable endothelial cells overexpressing human SLPI were generated from an endothelial cell line (EA.hy926). The cytoprotective effect was determined by cell survival assay. The results showed that endothelial-derived recombinant human SLPI (rhSLPI) reduced simulated ischemia/reperfusion (I/R)-(81.75% ± 1.42% vs. 60.27% ± 2.52%, p < 0.05) and hypoxia/reoxygenation (H/R)-induced EC injury (83.57% ± 1.78% vs. 63.07% ± 1.93%, p < 0.05). Moreover, co-culture of ECs overexpressing rhSLPI with CMs at ratios 1:1 and 1:3 or treatment with conditioned medium enhanced cell viability by 10.51–16.7% (co-culture) and 15.25–20.45% (conditioned medium) by reducing intracellular reactive oxygen species (ROS) production, the Bax/Bcl-2 expression ratio, caspase-3, and caspase-8, and in preconditioned CMs by activation of p38 MAPK and Akt survival kinase. In conclusion, this study showed for the first time that EC-derived rhSLPI provided cardio-vasculoprotective effects against I/R injury as a possible alternative therapeutic strategy for cardioprotection.

Non-communicable diseases (NCDs) are a worldwide health issue because of their prevalence, negative impacts on human welfare, and economic costs. Protease enzymes play important roles in viral and NCD diseases. Slowing disease progression by inhibiting proteases using small-molecule inhibitors or endogenous inhibitory peptides appears to be crucial.

Human cardiac microvascular endothelial cells (HCMECs) are sensitive to ischemia and vulnerable to damage during reperfusion. The release of damage-associated molecular patterns (DAMPs) during reperfusion induces additional tissue damage. The current study aimed to identify early protein DAMPs in human cardiac microvascular endothelial cells subjected to ischemia-reperfusion injury (IRI) using a proteomic approach and their effect on endothelial cell injury. HCMECs were subjected to 60 min of simulated ischemia and 6 h of reperfusion, which can cause lethal damage. DAMPs in the culture media were subjected to liquid chromatography-tandem mass spectrometry proteomic analysis. The cells were treated with endothelial IRI-derived DAMP medium for 24 h. Endothelial injury was assessed by measuring lactate dehydrogenase activity, morphological features, and the expression of endothelial cadherin, nitric oxide synthase (eNOS), and caveolin-1. The top two upregulated proteins, DNAJ homolog subfamily B member 11 and pyrroline-5-carboxylate reductase 2, are promising and sensitive predictors of cardiac microvascular endothelial damage. HCMECs expose to endothelial IRI-derived DAMP, the lactate dehydrogenase activity was significantly increased compared with the control group (10.15 ± 1.03 vs 17.67 ± 1.19, respectively). Following treatment with endothelial IRI-derived DAMPs, actin-filament dysregulation, and downregulation of vascular endothelial cadherin, caveolin-1, and eNOS expressions were observed, along with cell death. In conclusion, the early protein DAMPs released during cardiac microvascular endothelial IRI could serve as novel candidate biomarkers for acute myocardial IRI. Distinct features of impaired plasma membrane integrity can help identify therapeutic targets to mitigate the detrimental consequences mediated of endothelial IRI-derived DAMPs.

Background: Hypercholesterolemia is an independent modifiable risk factor that accelerates the development of both non-alcoholic fatty liver and atherosclerosis. Coconut water contains a variety of phytochemicals that make it appealing for producing vinegar. Coconut vinegar is rapidly gaining popularity for health benefits in Southeast Asia. The purpose of this study is to evaluate the effect of daily supplementation of coconut vinegar on hepatic and vascular oxidative stress in rats fed a high-cholesterol diet (HCD).Methods: Mature coconut water was fermented with coconut sap sugar using Saccharomyces cerevisiae and Acetobacter aceti vat Europeans, respectively. Bioactive compounds and antioxidant capacity of coconut vinegar were examined in vitro. Adult male Sprague–Dawley rats were randomly divided into four groups; the control group fed a standard diet (S), a group that received HCD (SC), a group that received HCD supplemented with coconut vinegar at a dose of 1 mL/kg/day (SCV), and a group that received HCD with atorvastatin at a dose of 30 mg/kg/day (SCA). After 8 weeks, serum metabolic profiles, fatty liver, hepatic, and vascular oxidative stress were determined.Results: In in vitro studies, coconut vinegar was rich in phenolic compounds and organic acids. The antioxidant capacity of 30 μL of coconut vinegar was 181.55 ± 8.15 μM Trolox equivalent antioxidant capacity (TEAC). In the HCD fed rats, daily supplementation of coconut vinegar reduced weight gain, serum triglycerides, and fasting blood sugar levels without renal or liver toxicity. In the liver, coconut vinegar reduced the accumulation of both hepatic cholesterol and hepatic triglyceride, and it also reduced hepatic 4-hydroxynonenal (4-HNE) lipid peroxidation. In the aortic tissues, coconut vinegar increased nitric oxide bioavailability and reduced aortic 4-HNE lipid peroxidation.Conclusion: Novel coconut vinegar is the source of antioxidants, and daily supplementation of coconut vinegar was found to attenuate dyslipidemia-induced hepatic and vascular oxidative stress by protective against cellular lipid peroxidation.