Oat protein modulates cholesterol metabolism and improves cardiac systolic function in high fat, high sucrose fed rats.

Oats are recognized to provide many health benefits that are mainly associated with its dietary fibre, ß-glucan. However, the protein derived from oats is largely understudied with respect to its ability to maintain health and attenuate risk factors of chronic diseases. The goal of the current study was to investigate the metabolic effects of oat protein consumption in lieu of casein as the protein source in high fat, high sucrose (HF/HS) fed Wistar rats. Four-week-old rats were divided into three groups and were fed three different experimental diets: a control diet with casein as the protein source, an HF/HS diet with casein, or an HF/HS diet with oat protein for 16 weeks. Heart structure and function were determined by echocardiography. Blood pressure measurements, an oral glucose tolerance test, and markers of cholesterol metabolism, oxidative stress, inflammation, and liver and kidney damage were also performed. Our study results show that incorporation of oat protein in the diet was effective in preserving systolic heart function in HF/HS fed rats. Oat protein significantly reduced serum total and low-density lipoprotein cholesterol levels. Furthermore, oat protein normalized liver HMG-CoAR activity, which, to our knowledge, is the first time this has been reported in the literature. Therefore, our research suggests that oat protein can provide hypocholesterolemic and cardioprotective benefits in a diet-induced model of metabolic syndrome.

Oat Beta-Glucan Alone and in Combination with Hydrochlorothiazide Lowers High Blood Pressure in Male but Not Female Spontaneously Hypertensive Rats.

Oats are considered a functional food due to the beneficial health effects associated with their consumption and are suitable to be explored for their ability to prevent or manage chronic disease, such as hypertension. Here, we examined the cardiovascular benefits of an oat beta-glucan extract in male and female spontaneously hypertensive rats (SHRs) to unravel its sex-specific roles when used with an anti-hypertensive medication, hydrochlorothiazide. Five-week-old male and female SHRs and Wistar-Kyoto (WKY) rats were treated with oat beta-glucan and hydrochlorothiazide for 15 weeks. Twenty-week-old male and female SHRs showed high blood pressure (BP), cardiac remodeling, and cardiac dysfunction. These animals also had significantly increased levels of malondialdehyde (MDA), angiotensin II, and norepinephrine. Treatments with beta-glucan and hydrochlorothiazide were able to differentially prevent high BP, cardiac dysfunction, and alterations in malondialdehyde (MDA), angiotensin II, and norepinephrine in 20-week-old male and female SHRs. To conclude, beta-glucan alone and in combination with hydrochlorothiazide may be a promising a strategy for managing hypertension and related cardiac complications.

Effects of blueberry polyphenolic extract on vascular remodeling in spontaneously hypertensive rats.

Blueberry is considered a functional food due to various beneficial health effects associated with its consumption. Therefore, we examined the cardiovascular benefits of a blueberry polyphenolic extract in spontaneously hypertensive rats (SHR). Male SHR and Wistar-Kyoto (WKY) rats were administered with blueberry polyphenolic extract for 15 weeks. SHR showed significant augmented media-to-lumen ratio compared to WKY rats and blueberry polyphenolic extract significantly improved media-to-lumen ratio. SHR also had high blood pressure (BP), cardiac remodeling, and diastolic dysfunction and treatment did not affect BP or cardiac structure and function. SHR showed significantly increased the levels of malondialdehyde (MDA) and blueberry polyphenolic extract did not lower MDA. The levels of interleukin 6 and nitrate/nitrite ratio were unaltered in SHR. SHR showed a significant increase in the pro-apoptotic marker, Bax. Blueberry polyphenolic extract significantly lowered Bax. Our study shows that blueberry polyphenolic extract is beneficial in preventing vascular remodeling and cardiac apoptosis. PRACTICAL APPLICATIONS: Similar to many other berries, blueberries are repertoire of many phytochemicals including polyphenols. Along with its considerably well-established role as a sought after berry, blueberries have been at the forefront of approaches to hharnessing health benefits from plant food sources. Several studies have attempted to unravel the role of blueberry and their major phytochemicals in reducing the risk of cardiovascular diseases and reported their beneficial effects. Our pre-clinical study found that blueberry polyphenolic extract can reduce vascular remodeling in the setting of hypertension. This new finding further suggests the potential of blueberry-based phytochemicals. Further exploration of blueberries and their phytochemicals and positive outcomes from such studies can lead to substantial benefits for consumers and economy as a whole.

Impact of oats in the prevention/management of hypertension.

Oats are a rich source of a soluble fibre, beta-glucan, phenolic compounds, as well as functional lipid and protein components that could potentially aid in preventing and managing hypertension. Processing techniques commonly used to manufacture oat based foods have been shown to improve its physiological efficacy. Hypertension is a common condition that is a risk factor for cardiovascular disease, a primary cause of mortality worldwide. Though exercise and pharmacological interventions are often used in the management of hypertension, diet is an incredibly important factor. One preclinical study and a handful of clinical studies have shown that oat components/products are effective in lowering blood pressure. However, research in this area is limited and more studies are needed to elucidate the anti-hypertensive potential of oats.

Potential Associations among Bioactive Molecules, Antioxidant Activity and Resveratrol Production in Vitis vinifera Fruits of North America.

Grapes (Vitis vinifera L.) are rich in bioactive molecules contributing to health benefits. Consumption of grapes is linked to reduced incidence of cardiovascular diseases. Studies on table grape cultivars are limited although much attention in research was focused on the wine industry. Bioactive effects of grapes as anti-inflammatory, anticarcinogenic, cardioprotective, vasorelaxant, phytoestrogenic and neuroprotective have also been reported. For example, resveratrol is a natural food ingredient present in grapes, with high antioxidant potential. Here we conducted an exploratory study to investigate bioactive molecules, antioxidant activity and the association between constitutive stilbene synthase (STS) gene expression and the resveratrol biosynthesis in selected table grape varieties in North America. The phenolic compounds, fatty acid composition and antioxidant activity of four grape varieties were compared. Red Globe variety was rich in unsaturated fatty acids as well as phenolic compounds such as caffeic acid, quercetin and resveratrol. Meanwhile, the constitutive expression of grape stilbene synthase gene was higher in Flame and Autumn Royal where resveratrol content of these cultivars was relatively low compared to the Red Globe variety. This study shows the potential links in grape antioxidant activity and resveratrol production, but more studies are necessary to show the association.

A Comprehensive Analysis of the Efficacy of Resveratrol in Atherosclerotic Cardiovascular Disease, Myocardial Infarction and Heart Failure.

Atherosclerosis, myocardial infarction (MI) and heart failure (HF) are the main causes of mortality and morbidity around the globe. New therapies are needed to better manage ischemic heart disease and HF as existing strategies are not curative. Resveratrol is a stilbene polyphenolic compound with favorable biological effects that counter chronic diseases. Current evidence suggests that resveratrol is cardioprotective in animal models of atherosclerosis, ischemic heart disease, and HF. Though clinical studies for resveratrol have been promising, evidence remains inadequate to introduce it to the clinical setting. In this narrative review, we have comprehensively discussed the relevant compelling evidence regarding the efficacy of resveratrol as a new therapeutic agent for the management of atherosclerosis, MI and HF.

Saskatoon berry supplementation prevents cardiac remodeling without improving renal disease in an animal model of reno-cardiac syndrome.

Saskatoon berry (SKB) may have the potential to counter reno-cardiac syndrome owing to its antioxidant capacity. Here, we investigated the renal and cardiovascular effects of SKB-enriched diet in a rat model of reno-cardiac disease. Two groups of wild-type rats (+/+) and two groups of Hannover Sprague-Dawley (Han:SPRD-Cy/+) rats were given either regular diet or SKB diet (10% w/w total diet) for 8 weeks. Body weight, kidney weight, kidney water content, and left ventricle (LV) weight were measured. Blood pressure (BP) was measured by the tail-cuff method. Echocardiography was performed to assess cardiac structure and function. Serum creatinine and malondialdehyde (MDA) were also measured. Han:SPRD-Cy/+ rats had significantly higher kidney weight, kidney water content, LV weight, BP, and creatinine compared with wild-type rats (+/+). The SKB diet supplementation did not reduce kidney weight, kidney water content, BP, and LV weight in Han:SPRD-Cy/+ rats. The SKB diet also resulted in higher systolic BP in Han:SPRD-Cy/+rats. Han:SPRD-Cy/+rats showed cardiac structural remodeling (higher LV wall thickness) without any cardiac functional abnormalities. Han:SPRD-Cy/+ rats also had significantly higher creatinine whereas the concentration of MDA was not different. The SKB diet supplementation reduced cardiac remodeling and the concentration of MDA without altering the concentration of creatinine in Han:SPRD-Cy/+ rats. In conclusion, Han:SPRD-Cy/+ rats developed significant renal disease, high BP, and cardiac remodeling by 8 weeks without cardiac functional impairment. The SKB diet may be useful in preventing cardiac remodeling and oxidative stress in Han:SPRD-Cy/+rats. PRACTICAL APPLICATIONS: Saskatoon berry (SKB) is widely consumed as fresh fruit or processed fruit items and has significant commercial value. It may offer health benefits due to the presence of bioactives such as anthocyanins. SKB has very good culinary flavors, and it is an economically viable fruit crop in many parts of the world. The disease-modifying benefits of SKB are mainly ascribed to the antioxidant nature of its bioactive content. Polycystic kidney disease is a serious condition that can lead to renal and cardiac abnormalities. Here, we showed that SKB supplementation was able to mitigate cardiac remodeling and lower the level of a marker of oxidative stress in an animal model of reno-cardiac syndrome. Our study suggests that SKB possesses beneficial cardioprotective properties. Further evidence from human studies may help in increasing the consumption of SKB as a functional food.

Comparative and Combinatorial Effects of Resveratrol and Sacubitril/Valsartan alongside Valsartan on Cardiac Remodeling and Dysfunction in MI-Induced Rats.

The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis.

The effects of oat ingredients on blood pressure in spontaneously hypertensive rats.

This study investigated the blood pressure (BP) lowering and cardioprotective effects of oat avenanthramide C and beta-glucan alone or in combination in spontaneously hypertensive rats (SHR). Five-weeks-old male SHR and Wistar-Kyoto rats received vehicle, avenanthramide C and beta-glucan alone or a combination of avenanthramide C and beta-glucan via gavage for 15 weeks. BP was measured at 0, 10, and 15 weeks of treatment. Echocardiography was performed at 15 weeks of treatment. Oxidative stress and inflammation were also measured. Beta-glucan alone prevented the increase in systolic and diastolic BP in SHR, but avenanthramide C alone or the combination did not prevent the increase in systolic and diastolic BP. SHRs treated with beta-glucan and not avenanthramide C or the combination reduced isovolumetric relaxation time when compared to SHR treated with vehicle. Beta-glucan and avenanthramide C decreased the levels of malondialdehyde, a marker of oxidative stress in SHR. In conclusion, beta-glucan is a potential antihypertensive agent that may alleviate cardiovascular abnormalities. PRACTICAL APPLICATIONS: Oats products are believed to contain many bioactives that possess potential beneficial properties against chronic diseases. Specifically, oats beta-glucan has been well-established for its efficacy in positively modulating the risk factor for dyslipidemia. This preliminary in vivo study shows that beta-glucan is a potential antihypertensive agent that may alleviate cardiac dysfunction as well. In light of the current findings, further human studies may establish the efficacy of oats beta-glucan in hypertensive patients alongside the current antihypertensive medications. This novel attribute established via rigorous studies may provide an impetus for oats products and oats industry. Last but not least, it will also help improve the cardiovascular disease burden in a cost-effective way.

Efficacy and Safety of Resveratrol in Type 1 Diabetes Patients: A Two-Month Preliminary Exploratory Trial.

Resveratrol has been reported to be beneficial against diabetes complications. The objective of this study was to evaluate the efficacy of resveratrol in decreasing hyperglycemia in patients with type 1 diabetes (T1D) by a preliminary investigation designed as an exploratory clinical trial. Thirteen patients with T1D from both the sexes participated in this trial. All patients received resveratrol in 500 mg capsules, twice daily for 60 days. Bodyweight, fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, homeostasis model of assessment for insulin resistance (HOMA-IR), homeostasis model of assessment for ß-cell function (HOMA-ß), and markers of liver and kidney damage, inflammation, and oxidative stress were measured before the intervention, at 30 days and at 60 days. Resveratrol supplementation for 60 days significantly decreased FBS and HbA1c in comparison with the baseline values. Resveratrol treatment also resulted in a decrease in the level of a marker for oxidative stress, malondialdehyde, and an increase in total antioxidant capacity in T1D patients. Insulin, HOMA-IR, HOMA-ß, and markers of liver and kidney function and inflammation were not significantly affected by resveratrol treatment. Overall, the results showed that 60 days of resveratrol supplementation exerted strong antidiabetic and antioxidant effects in patients with T1D.

Resveratrol prevents palmitic-acid-induced cardiomyocyte contractile impairment.

Long-chain saturated fatty acids, especially palmitic acid (PA), contribute to cardiomyocyte lipotoxicity. This study tests the effects of PA on adult rat cardiomyocyte contractile function and proteins associated with calcium regulating cardiomyocyte contraction and relaxation. Adult rat cardiomyocytes were pretreated with resveratrol (Resv) and then treated with PA. For the reversal study, cardiomyocytes were incubated with PA prior to treatment with Resv. Cardiomyocyte contractility, ratio of rod- to round-shaped cardiomyocytes, and Hoechst staining were used to measure functional and morphological changes in cardiomyocytes. Protein expression of sarco-endoplasmic reticulum ATPase 2a (SERCA2a), native phospholamban (PLB) and phosphorylated PLB (pPLB ser16 and pPLB thr17), and troponin I (TnI) and phosphorylated TnI (pTnI) were measured. SERCA2a activity was also measured. Our results show that PA (200 µM) decreased the rate of cardiomyocyte relaxation, reduced the number of rod-shaped cardiomyocytes, and increased the number of cells with condensed nuclei; pre-treating cardiomyocytes with Resv significantly prevented these changes. Post-treatment with Resv did not reverse morphological changes induced by PA. Protein expression levels of SERCA2a, PLB, pPLBs, TnI, and pTnI were unchanged by PA or Resv. SERCA2a activity assay showed that Vmax and Iono ratio were increased with PA and pre-treatment with Resv prevented this increase. In conclusion, our results show that Resv protect cardiomyocytes from contractile dysfunction induced by PA.

Dietary flaxseed protects against ventricular arrhythmias and left ventricular dilation after a myocardial infarction.

Dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been associated with a lower incidence of cardiovascular events and sudden cardiac death. Flaxseed is a rich plant source of n-3 PUFAs and can retard the progression and accelerate the regression of atherosclerotic plaques. The aim of the study was to examine the preventive and therapeutic effects of dietary flaxseed on arrhythmias and heart dysfunction that develops after a myocardial infarction (MI). The left anterior descending coronary artery was ligated in rats to induce the MI. Rats were randomized into five groups: sham MI with normal chow, MI with normal chow, MI with 10% milled flaxseed supplementation (flax), MI with 4.4% supplemented flax oil enriched in alpha-linolenic acid (ALA) and MI with flax lignan secoisolariciresinol diglucoside (SDG) supplementation (0.44%). Animals were fed with their respective diets for 2 weeks before and for 8 weeks after the surgery. Echocardiography and continuous electrocardiographic recordings were obtained after ligation to confirm the induction of the MI, to check for arrhythmias and to assess cardiac function. Histological examination was also performed to evaluate cardiac fibrosis. Dietary supplementation with flaxseed, ALA or SDG before and after the induction of the MI significantly reduced the incidence of arrhythmias and resulted in significantly smaller infarct size, less left ventricle dilation, and decreased myocardial fibrosis and tumor necrosis factor-α levels compared to the control MI group. Together, this study supports a beneficial effect of dietary flaxseed in patients for the prevention and treatment of arrhythmias and ventricular remodeling post-MI.

Ginseng Berry Extract Rich in Phenolic Compounds Attenuates Oxidative Stress but not Cardiac Remodeling post Myocardial Infarction.

The cardioprotective effects of ginseng root extracts have been reported. However, nothing is known about the myocardial actions of the phenolic compounds enriched in ginseng berry. Therefore, this study was undertaken to investigate the effects of American ginseng berry extract (GBE) in an experimental model of myocardial infarction (MI). Coronary artery ligation was performed on Sprague⁻Dawley male rats to induce MI after which animals were randomized into groups receiving either distilled water or GBE intragastrically for 8 weeks. Echocardiography and assays for malondialdehyde (MDA) and TNF-α were conducted. Flow cytometry was used to test the effects of GBE on T cell phenotypes and cytokine production. Although GBE did not improve the cardiac functional parameters, it significantly attenuated oxidative stress in post-MI rat hearts. GBE treatment also resulted in lower than control levels of TNF-α in post-MI rat hearts indicating a strong neutralizing effect of GBE on this cytokine. However, there was no effect of GBE on the proportion of different T cell subsets or ex-vivo cytokine production. Taken together, the present study demonstrates GBE reduces oxidative stress, however no effect on cardiac structure and function in post-MI rats. Moreover, reduction of TNF-α levels below baseline raises concern regarding its use as prophylactic or preventive adjunct therapy in cardiovascular disease.

The Effects of Resveratrol in Patients with Cardiovascular Disease and Heart Failure: A Narrative Review.

Cardiovascular disease (CVD) is the main cause of death globally and responsible for the second highest number of deaths in Canada. Medical advancements in the treatment of CVD have led to patients living longer with CVD but often progressing to another condition called heart failure (HF). As a result, HF has emerged in the last decade as a major medical concern. Fortunately, various "traditional" pharmacotherapies for HF exist and have shown success in reducing HF-associated mortality. However, to augment the treatment of patients with CVD and/or HF, alternative pharmacotherapies using nutraceuticals have also shown promise in the prevention and treatment of these two conditions. One of these natural compounds considered to potentially help treat HF and CVD and prevent their development is resveratrol. Herein, we review the clinical findings of resveratrol's ability to be used as an effective treatment to potentially help treat HF and CVD. This will allow us to gain a more fulsome appreciation for the effects of resveratrol in the health outcomes of specific patient populations who have various disorders that constitute CVD.

Are the cardioprotective effects of the phytoestrogen resveratrol sex-dependent? 1.

Cardiovascular disease (CVD) is the number one cause of death in both men and women. Younger women have a lower risk for CVD, but their risk increases considerably after menopause when estrogen levels decrease. The cardiovascular protective properties of estrogen are mediated through decreasing vascular inflammation and progression of atherosclerosis, decreasing endothelial cell damage by preventing apoptosis and anti-hypertrophic mechanisms. Estrogen also regulates glucose and lipid levels, which are 2 important risk factors for CVD. Resveratrol (RES), a cardioprotective polyphenolic compound, is classified as a phytoestrogen due its capacity to bind to and modulate estrogen receptor signalling. Due to its estrogen-like property, we speculate that the cardioprotective effects of RES treatment could be sex-dependent. Based on earlier reports and more recent data from our lab presented here, we found that RES treatment may have more favourable cardiovascular outcomes in females than in males. This review will discuss estrogen- and phytoestrogen-mediated cardioprotection, with a specific focus on sex-dependent effects reported in preclinical and clinical studies.

Effects of N-acetyl cysteine and melatonin on early reperfusion injury in patients undergoing coronary artery bypass grafting: A randomized, open-labeled, placebo-controlled trial.

OBJECTIVES: This study assessed the efficacy of oral consumption of N-acetyl cysteine (NAC) and melatonin (ML) in reducing early reperfusion injury and acute oxidative stress in patients undergoing coronary artery bypass grafting (CABG) with respect to the measurements of cardiac troponin I, lactate, malondealdehyde (MDA), and tumor necrosis factor-α (TNF-α) levels in the blood. METHODS: This study was a randomized, open-label, placebo-controlled trial. Eighty eight patients, aged between 39 to 76 years and eligible for CABG, were recruited and randomly assigned into 3 intervention groups through a simple randomization method and underwent CABG surgery. Blood samples were withdrawn from arterial line, before the induction of anesthesia (before the start of surgery), after incision (before aortic cross-clamping), during global ischemia (during aortic cross-clamping), after aortic cross-clamping (on set of reperfusion), 15 minutes after reperfusion, and after recovery at the intense care unit. The blood samples were analyzed for troponin I, lactate, MDA and TNF-α levels. RESULTS: There was no significant difference in influencing variables among the groups at the baseline. Overall mean troponin I, lactate, and TNF- α levels were significantly different between the intervention groups (all P < .001) at the recovery phase. Post-hoc pairwise comparisons showed that the differences of mean serum levels between ML and control groups were statistically significant for MDA, TNF- α, lactate, and troponin I (P < .001, P = .001, and P = .001, respectively). The differences between NAC and control groups and between ML and NAC groups were only significant for mean lactate level (P < .001). CONCLUSION: The current study revealed that ML and NAC are potent antioxidants with similar efficacy in terms of reducing CABG related cardiac injury and oxidative stress with the dosage employed for the intervention.

Supplementation of Type 1 Diabetic Rats with Carrot Powder Lowers Blood Glucose without Improving Cardiac Structure and Function.

Foods and food bioactives have shown to be effective in preventing some human disease conditions. In this study, we examined the effects of carrot powder, rich in carotenoids, as a dietary supplement for the prevention of cardiac anomalies in streptozotocin (STZ) induced type 1 diabetic rats. Male Wistar rats were fed either control or carrot powder containing diet for 3 weeks. Type 1 diabetes was induced with STZ injection (65 mg/kg body weight) in half of the rats in each group. All rats were continued on their respective diet for a further 9 weeks. Cardiac structural and functional parameters were measured using echocardiography at 8 weeks post STZ administration. In comparison to non-diabetic rats, diabetic rats showed significant increase in isovolumetric relaxation time and a significant decrease in systolic function parameter, cardiac output. Left ventricular internal dimension and left ventricular posterior wall thickness were significantly higher in diabetic animals. Blood glucose levels were significantly lower in carrot supplemented diabetic rats when compared with non-treated diabetic rats. Diabetic rats treated and untreated had elevated level of lipid peroxidation. Catalase levels were significantly elevated in the carrot powder supplemented diabetic rats when compared to the control rats. Carrot supplementation lowered blood glucose levels significantly but did not normalize it to control levels. It had no effect on cardiac abnormalities and anti-oxidant status in rats with type 1 diabetes.

Cyanidin 3-O-glucoside prevents the development of maladaptive cardiac hypertrophy and diastolic heart dysfunction in 20-week-old spontaneously hypertensive rats.

The present study investigated the effects of cyanidin 3-O-glucoside (C3G) in cardiomyocytes (CM) and fibroblasts exposed to endothelin 1 (ET1), as well as in the spontaneously hypertensive rat (SHR) model, alone or in combination with hydrochlorothiazide (HCT). Adult rat CM and cardiac fibroblasts (CF) were pretreated with C3G and co-incubated with ET1 (10-7 M) for 24 hours. Five-week-old male SHR and their normotensive controls, Wistar-Kyoto rats (WKY), received one of 4 treatments via oral gavage daily for 15 weeks: (1) water (control); (2) C3G (10 mg per kg per day); (3) HCT (10 mg per kg per day); (4) C3G + HCT (10 mg per kg per day each). Blood pressure (BP) was measured at 1, 8 and 15 weeks. Echocardiography measurements were performed at 15 weeks. C3G prevented ET1-induced CM death and hypertrophy. Stimulating CF with ET1 did not induce their phenoconversion; nevertheless, C3G inhibited un-stimulated CF differentiation. HCT slowed the rise of systolic BP (SBP) in the SHR over time (week 1: SHRs control = 161 ± 6.3 mmHg, SHRs HCT = 129 ± 6.3 mmHg; week 15: SHRs control = 201 ± 7.3 mmHg, SHRs HCT = 168 ± 7.3 mmHg), but C3G had no effect on SBP (week 1: SHRs control = 161 ± 6.3 mmHg, SHRs C3G = 126 ± 6.3 mmHg; week 15: SHRs control = 201 ± 7.3 mmHg, SHRs C3G = 186 ± 7.3 mmHg). SHRs treated with C3G, HCT, and C3G + HCT had lower left ventricular mass and shorter isovolumetric relaxation time compared to control SHRs. C3G ameliorated cardiac hypertrophy and diastolic dysfunction in SHRs.

Effects of cyanidin 3-0-glucoside on cardiac structure and function in an animal model of myocardial infarction.

Cyanidin 3-0-glucoside (CG) is a polyphenol with potential health benefits. In this study, we investigated, for the first time, the cardioprotective effects of CG in an animal model of myocardial infarction (MI), a major cause of death worldwide. Sham and MI rats were administered CG (10 mg kg-1 day-1) daily for one week prior to surgery, and 8 weeks post-surgery. Echocardiography was performed to assess cardiac structure and function at 4 and 8 weeks. At 4 weeks, MI rats had significantly lower body mass when compared to control rats, and CG administration significantly prevented this decrease. Four-week MI rats also showed significantly increased left ventricle dilation, end systolic and end diastolic volumes in comparison to controls, and CG significantly prevented these adverse changes. Ejection fraction was significantly lower in 4-week MI rats in comparison to controls, and CG had no effect on this parameter. At 8 weeks, body mass was significantly lower in MI rats when compared to control rats, and CG significantly prevented this decrease. At 8 weeks, MI rats showed a significant increase in left ventricle dilation and isovolumic relaxation time, while ejection fraction was significantly lower when compared to controls; these parameters were not altered by CG treatment. Eight-week MI rats had significantly higher level of oxidative stress in heart tissue in comparison to controls, and CG administration did not prevent this increase. In conclusion, administration of CG was able to significantly preserve body mass in both 4 and 8 weeks MI rats, as well as significantly prevent cardiac dilation in 4 weeks MI rats. However, CG was unable to sustain this cardioprotection, as cardiac structure and function were not significantly improved in 8 weeks MI rats.

Disparate Effects of Stilbenoid Polyphenols on Hypertrophic Cardiomyocytes In Vitro vs. in the Spontaneously Hypertensive Heart Failure Rat.

Stilbenoids are bioactive polyphenols, and resveratrol (trans-3,5,40-trihydroxystilbene) is a representative stilbenoid that reportedly exerts cardioprotective actions. As resveratrol exhibits low oral bioavailability, we turned our attention to other stilbenoid compounds with a history of medicinal use and/or improved bioavailability. We determined the effects of gnetol (trans-3,5,20,60-tetrahydroxystilbene) and pterostilbene (trans-3,5-dimethoxy-40-hydroxystilbene) on cardiac hypertrophy. In vitro, gnetol and pterostilbene prevented endothelin-1-induced indicators of cardiomyocyte hypertrophy including cell enlargement and protein synthesis. Gnetol and pterostilbene stimulated AMP-activated protein kinase (AMPK), and inhibition of AMPK, using compound C or shRNA knockdown,abolished these anti-hypertrophiceffects. In contrast,resveratrol, gnetol, nor pterostilbene reduced blood pressure or hypertrophy in the spontaneously hypertensive heart failure (SHHF) rat. In fact, AMPK levels were similar between Sprague-Dawley and SHHF rats whether treated by stilbenoids or not. These data suggest that the anti-hypertrophic actions of resveratrol (and other stilbenoids?) do not extend to the SHHF rat, which models heart failure superimposed on hypertension. Notably, SHHF rat hearts exhibited prolonged isovolumic relaxationtime(an indicator of diastolicdys function),and this was improved by stilbenoid treatment.In conclusion, stilbenoid-based treatment as a viable strategy to prevent pathological cardiac hypertrophy,a major risk factor for heart failure,may be context-dependent and requires furtherstudy.