scholarly journals Cardiovascular Protective Effects of Salvianic Acid A on db/db Mice with Elevated Homocysteine Level

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Lei Gao ◽  
Parco M. Siu ◽  
Shun-wan Chan ◽  
Christopher W. K. Lai
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Mouse Liver ◽  
Ventricular Hypertrophy ◽  
Homocysteine Level ◽  
Redox Status ◽  
Left Ventricular ◽  
Protective Effects ◽  
Elevated Blood ◽  
Diabetic Mice

The onsets of left ventricular hypertrophy (LVH) and endothelial dysfunction (ED) in diabetics, especially in those with elevated homocysteine (Hcy), precede the development of cardiovascular (CV) events. Salvianic acid A (SAA) is a renowned Traditional Chinese Medicine (TCM) that has been applied in the treatment of cardiovascular disease for many decades. In this study, we aimed (1) to investigate the CV protective effects of SAA on ameliorating LVH and ED in db/db mice with elevated blood Hcy level and (2) to decipher whether the observed CV protective effects of SAA are associated with Hcy metabolism by modulating the methylation potential and redox status in the liver of the db/db mice with elevated blood Hcy level. Our results found that the administration of SAA could significantly slow down the build-up of left ventricular mass and ameliorate ED. Immunological assay analysis on the mouse liver tissue also indicated that SAA treatment on db/db mice with elevated Hcy was associated with reduced methylation potential but improved redox status. In conclusion, we revealed that SAA has the potential to protect against the hyperglycemia- and hyperhomocysteinemia-induced oxidative stress on diabetic mice via modulation in Hcy metabolism.

Abstract 1582: Adenosine A3 Receptor Deficiency Exerts Unanticipated Protective Effects on Pressure Overloaded-Induced Left Ventricular Hypertrophy and Dysfunction in Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Zhongbing Lu ◽  
John Fassett ◽  
Xin Xu ◽  
Xinli Hu ◽  
Guangshuo Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Heart Association ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Protective Effects ◽  
Rat Cardiomyocytes ◽  
Extracellular Adenosine ◽  
Myocardial Oxidative Stress

Endogenous adenosine can protect the overloaded heart against the development of hypertrophy and heart failure, but the contribution of A 1 receptors (A 1 R) and A 3 receptors(A 3 R) is not known. To test the hypothesis A 1 R and A 3 R can protect the heart against systolic overload, we exposed A 3 R gene deficient (A 3 R KO) mice and A 1 R KO mice to transverse aortic constriction (TAC). Contrary to our hypothesis, A 3 R KO attenuated 5 weeks TAC-induced left ventricular (LV) hypertrophy (ratio of ventricular mass/body weight increased to 7.6 ±0.3 mg/g in wild type (Wt) mice as compared with 6.3±0.4 mg/g in KO), fibrosis and dysfunction (LV ejection fraction decreased to 43±2.5% and 55±4.2% in Wt and KO mice, respectively). A 3 R KO also attenuated the TAC-induced increases of myocardial ANP and the oxidative stress markers 3-nitrotyrosine(3-NT ) and 4-hydroxynonenal. In addition, A 3 R KO significantly attenuated TAC-induced activation of multiple MAP kinase pathways, and the activation of Akt-GSK signaling pathway. In contrast, A 1 R-KO increased TAC-induced mortality, but did not alter ventricular hypertrophy or dysfunction compared to Wt mice. In mice in which extracellular adenosine production was impaired by CD73 KO, TAC caused greater hypertrophy and dysfunction, and increased myocardial 3-NT, indicates that extracellular adenosine protects heart against TAC-induced ventricular oxidative stress and hypertrophy. In neonatal rat cardiomyocytes induced to hypertrophy with phenylephrine, the adenosine analogue 2-chloroadenosine (CADO) reduced cell area, protein synthesis, ANP and 3-NT. Antagonism of A3R significantly potentiated the anti-hypertrophic effects of CADO. Our data demonstrated that extracellular adenosine exerts protective effects on the overloaded heart, but A 3 R act counter to the protective effect of adenosine. The data suggest that selective attenuation of A 3 R activity might be a novel approach to attenuate pressure overload-induced myocardial oxidative stress, LV hypertrophy and dysfunction. This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).

scholarly journals The Role of Oxidative Stress and Inflammation in Cardiovascular Aging

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Junzhen Wu ◽  
Shijin Xia ◽  
Bill Kalionis ◽  
Wenbin Wan ◽  
Tao Sun
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Low Grade ◽  
Oxygen Species ◽  
Age Related ◽  
Vascular Elasticity ◽  
Low Grade Inflammation

Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66Shc, and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol.

Abstract 11598: Increased Advanced Glycation End-Products Accelerate the Progress of Left Ventricular Hypertrophy Under Condition of Elevated Oxidative Stress or Insulin Resistance in Patients With Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Aoyama Akihiro ◽  
Masuda Takashi ◽  
Ogura Misao ◽  
Shimizu Ryosuke ◽  
Kato Michitaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Clinical Characteristics ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
One Year ◽  
Observation Period

Background: Elevated oxidative stress or insulin resistance has been shown to promote the production of advanced glycation end-products (AGEs) in patients with hypertension (HT). Because AGEs enhance left ventricular hypertrophy (LVH) via the activation of nuclear factor-kappa B, it is considered that increased AGEs contribute to LVH in HT patients. The aim of this study was to investigate the effect of increased AGEs on LVH in them. Methods: Eighty five HT patients aged 65 ± 9 years were prospectively followed up for a year, whose blood pressure was controlled under 140/90mmHg. We assessed patients’ glucose and lipid metabolism and neurohumoral factors including plasma noradrenaline and renin activity as clinical characteristics. We measured serum malondialdehyde-modified LDL-cholesterol (MDA-LDL) and plasma pentosidine as parameters of oxidative stress and AGEs, respectively. Homeostasis model assessment ratio (HOMA-R), estimate glomerular filtration rate (eGFR) and left ventricular mass index (LVMI) were assessed as parameters of insulin resistance, renal function and LVH, respectively. All parameters were assessed before and after one-year observation period. We examined the change in each parameter from baseline to the value measured after the observation period ([[Unable to Display Character: &#8895;]]MDA-LDL, [[Unable to Display Character: &#8895;]]pentosidine, [[Unable to Display Character: &#8895;]]HOMA-R and [[Unable to Display Character: &#8895;]]LVMI). We divided patients into two groups based on the median of baseline pentosidine: high AGEs and low AGEs groups. We compared baseline values between the two groups. We analyzed the relationships among [[Unable to Display Character: &#8895;]]MDA-LDL, [[Unable to Display Character: &#8895;]]HOMA-R, [[Unable to Display Character: &#8895;]]Pentosidine and [[Unable to Display Character: &#8895;]]LVMI, and performed stepwise multiple regression analysis using parameters of clinical characteristics and AGEs to detect the predictors for the LVH progress after one year. Results: Baseline LVMI was significantly higher in the high AGEs group than in the low AGEs group (P<0.05). [[Unable to Display Character: &#8895;]]Pentosidine was positively correlated with [[Unable to Display Character: &#8895;]]MDA-LDL (r=0.34, P<0.01),[[Unable to Display Character: &#8895;]]HOMA-R (r=0.37, P<0.01) and [[Unable to Display Character: &#8895;]]LVMI (r=0.39, P<0.05). Multiple regression analysis detected pentosidine as a significant independent predictor for the LVH progress (β=0.407, P=0.005) (R2=0.315). Conclusion: Increased AGEs accelerated the LVH progress under condition of elevated oxidative stress or insulin resistance in HT patients.

Abstract P175: Can Pediatric Hypertension Criteria be Simplified? A Prediction Analysis of Subclinical Cardiovascular Outcomes From the Bogalusa Heart Study

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Bo Xi ◽  
Tao Zhang ◽  
Shengxu Li ◽  
Wei Shen ◽  
Emily Harville ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Characteristic Curve ◽  
Later Life ◽  
Left Ventricular ◽  
Pediatric Hypertension ◽  
Bogalusa Heart Study ◽  
Heart Study ◽  
Subclinical Cardiovascular Disease

Background: Pre-hypertension and hypertension in childhood are defined by sex-, age- and height-specific 90th (or ≥120/80 mmHg) and 95th percentiles of blood pressure (BP), respectively, by the 2004 Fourth Report. However, these cut-offs are complex and cumbersome for use. This study assessed the performance of a simplified BP definition to predict adult hypertension and subclinical cardiovascular disease. Methods: The longitudinal cohort consisted of 1,225 adults (530 males, aged 26.3–47.7 years) from the Bogalusa Heart Study, with 27.1 years follow-up since childhood. We used 110/70 and 120/80 mmHg for children (age 6-11 years), and 120/80 and 130/85 mmHg for adolescents (age 12-17 years) as the simplified definitions of childhood pre-hypertension and hypertension, respectively, to compare with the complex definitions. Adult carotid intima-media thickness (CIMT), pulse wave velocity (PWV), and left ventricular mass were measured using digital ultrasound instruments. High CIMT was defined as being above the age-, gender- and race-specific 80th percentile, high PWV as being above the age-, gender-, race- and heart rate-specific 80th percentile and left ventricular hypertrophy as >46.7 g/m 2.7 in women and >49.2 g/m 2.7 in men. Results: Compared to normal BP, childhood hypertensives diagnosed by the simplified definition (4.1%, 50/1,225) and the complex definition (4.8%, 59/1,225) were both at higher risk of adult hypertension with hazard ratio=3.1 (95% confidence interval=1.8-5.3) by the simplified definition and 3.2 (2.0-5.0) by the complex definition, high PWV with 3.5 (1.7-7.1) and 2.2 (1.2-4.1), high CIMT with 3.1 (1.7-5.6) and 2.0 (1.2-3.6), and left ventricular hypertrophy with 3.4 (1.7-6.8) and 3.0 (1.6-5.6). The prediction using the two childhood BP definitions for adult hypertension and subclinical cardiovascular disease was also assessed by reclassification or receiver operating characteristic curve analyses. Conclusions: The simplified childhood BP definition predicts the risk of adult hypertension and subclinical cardiovascular disease equally as the complex definition does. The simplified pediatric BP cut-offs could be easier to use for screening children at high risk and for targeting early life interventions to reduce the risk of developing cardiovascular disease in later life.

Abstract 300: Alda-1 Attenuates Acute Ischemia-reperfusion Mediated Cardiac Damage in Aldehyde Dehydrogenase 2 Mutant Diabetic Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Guodong Pan
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Acute Ischemia ◽  
Protective Effects ◽  
Diabetic Mice ◽  
Aldehyde Dehydrogenase 2 ◽  
Cardiac Damage ◽  
Western Blots

Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme in heart, can remove 4-hydroxy-2-nonenal (4-HNE), a toxic by-products of oxidative stress induced by diabetes and ischemia-reperfusion (I/R) injury. A common inactivating mutation of ALDH2 (termed ALDH2*2) was found in 8% of the world’s population, which causes lower ALDH2 activity in mutation carriers. We hypothesized that Alda-1, the only known activator of both ALDH2 and ALDH2*2 mutation, is able to protect heart from I/R injury in diabetic mice with/without ALDH2*2 mutation. Adult male ALDH2*2 mutant and C57B6 wild-type (WT) mice at 3-4 months of age were made hyperglycemic with streptozotocin injection (150 mg/kg. i.p.). Three weeks after injection, Alzet osmotic pumps were implanted subcutaneously to deliver Alda-1 (10 mg/kg) or vehicle. Mice were sacrificed after one day of pump implantation. Hearts were isolated and subjected to 30-minute ischemic followed by 90-minute reperfusion in a Langendorff apparatus. The basal myocardial ALDH2 activity in diabetic ALDH2*2 mutant was significantly lower than in diabetic WT mice (0.50±0.23 vs 0.83±0.08 mmol/min/μg, -39.8%, p<0.05). Alda-1 significantly increased myocardial ALDH2 activity in both ALDH2*2 (1.17±0.38 mmol/min/μg, +134.0%, p<0.05) and WT (1.46±0.40 mmol/min/μg, +75.9%, p<0.05) diabetic mice. Compared with vehicle, Alda-1 significantly improved left ventricular pressure (LVP), and decreased infarcted areas (IA) both in ALDH2*2 (LVP: 4.30±2.03 vs 15.77±8.99 mmHg, +266.7%, p<0.05; IA: 75.17%±9.49 vs 40.46%±7.20, -46.2%, p<0.05) and WT (LVP: 14.22±7.92 vs 21.96±4.32 mmHg, +54.4%, p<0.05; IA: 42.44%±8.60 vs 28.61%±8.55, -32.6%, p<0.05) subjected to I/R injury. Western-blots showed that Alda-1 decreased levels of 4-HNE protein adducts, and increased levels of mitochondrial complex V in both ALDH2*2 and WT mice. Our data suggest that one-day Alda-1 treatment can confer cardio-protective effects against I/R injury in ALDH2*2 diabetic mice possibly accelerating the detoxification of toxic 4-HNE and thereby protecting mitochondria.

“ A STUDY OF CARDIOVASCULAR ABNORMALITY IN HYPERTENSIVE PATIENTS”

2021 ◽  
pp. 23-26
Author(s):  
Balendra Shekhar Deepankar ◽  
Saurabh Singh Thakur ◽  
Vimlesh Patidar
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Risk Factor ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Study Group ◽  
Hypertensive Patients ◽  
Cardiovascular Abnormality ◽  
Artery Disease

Introduction: Hypertension is a common health problem in developed countries and a major risk factor for cardiovascular diseases. Hypertension exhibits an iceberg phenomenon where unknown morbidity exceeds the known morbidity. Genetic and environmental factors are also reported to play a key role in hypertension, 90% of which are better classied as idiopathic. The cause of cardiovascular diseases in the hypertensive patient is blood pressure raised which is present chronically however the cause of elevated BP are different. In adults, 90% of hypertension cases are of essential hypertension .The Remaining 10% of hypertension cases with chronically elevated BP accounts for secondary cause. In hypertensive patient, the risk of cardiovascular disease is increases in men and women. Hypertension and diabetes mellitus are among the most common chronic non-communicable diseases and multifactorial disorders affecting both developed and developing countries and occur at a higher prevalence in the older age group and result from both genetic and environmental etiological factors. The aim of Study of Cardiovascular Abnormality in the Hypertension Patient. Methods: A prospective observational study consists of 95 cases of hypertension is undertaken to study the cardiovascular abnormality by ECG and ECHO. The study will be conducted on patients suffering from hypertension. A written informed consent will be taken from all the patients who are included in study group. All the data of the patients will be recorded on a pretested Performa. Preliminary data like name, age, sex, occupation, residence, date will be recorded. Detailed lipid prole study will be done to nd the correlation in patients with hypertension. All data will be statistically analyzed. Results: Out of 95 cases in the study group, 51 were female cases and 44 were males, 31 cases (7th decade), 40 cases (6th decade), 14 cases (5th decade), 8 cases(4th decade), 2 cases (< 3rd decade). Abnormal ECG changes which constitutes 85 patients, ST elevation was present in 12 patients and T-wave inversion was present in 47 patients, followed by 16 patients were shows left ventricular hypertrophy, 8 cases of cardiomyopathy which shows low voltage complexes. Coronary artery disease was predominant nding in the patients of hypertensive cardiovascular disease which was present in 54 cases out of 95 cases, of which 31 were male patients and 23 were female patients. CAD in hypertension (57%), the incidence of CAD was more in elderly and other abnormalities in hypertensive patients were left ventricular hypertrophy(11.6%), heart failure{due to cardiomyopathy(8.2%) and CAD} and valvular heart disease(4.2%). Conclusion: Cardiovascular abnormality in hypertensive patients encompasses a broad spectrum including coronary artery disease, asymptomatic LVH (either a concentric or an eccentric pattern) and clinical heart failure (with either a preserved or a reduced LVEF) stroke, heart failure, cardiomyopathy, arrhythmia, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis. Elderly age, smoking habits, chronic alcoholism and long standing history of DM have emerged as important risk factor for cardiovascular disease in hypertensive patients.

scholarly journals A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the MET-REMODEL trial

2019 ◽  
Vol 40 (41) ◽  
pp. 3409-3417 ◽  
Author(s):  
Mohapradeep Mohan ◽  
Shaween Al-Talabany ◽  
Angela McKinnie ◽  
Ify R Mordi ◽  
Jagdeep S S Singh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Coronary Artery Disease ◽  
Body Weight ◽  
Coronary Artery ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Haemoglobin A1c ◽  
Metformin Treatment ◽  
Artery Disease

Abstract Aim We tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes. Methods and results We randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference −1.37 (95% confidence interval: −2.63 to −0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study. Conclusion Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials.

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