29 research outputs found

    Circulating myostatin is reduced with aging in humans but not altered by short-term, high intensity training

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    Introduction: Ageing involves a loss of muscle mass and function. The rate of decline is associated with negative health outcomes and increased mortality (1). Muscle atrophy is observed at a predictable rate from 30 years of age (2), however maintenance of function is seen in masters athletes > 60 years of age (3). Myostatin acts as a negative regulator of muscle mass (4) and underlies hypertrophy with chronic resistance training (5) and atrophy in chronic conditions (4). Experiment 1: Declared healthy participants (n = 83, 18 - 75 years of age, 36 male, 47 female) were recruited. Body composition, metabolic rate, grip strength and 6-minute walk test were recorded. Venous blood was collected and total myostatin concentration (herein referred to as myostatin) quantified by enzyme-linked immunosorbent assay. Total myostatin was lower in females compared with males (2176.1 [135.3] vs. 2788.7 [180.2] pg.mL-1 [p = 0.007]). Stepwise regression observed that myostatin concentration is best predicted firstly by gender, then by age (r = 0.399, p = 0.02), and was not further improved by the addition of measures of metabolism, muscle mass or function. Experimental 2: A cohort of aged sedentary (SED) males (n = 14; 63.9 [5.6] years of age) and masters athletes (lifelong exerciser [LEX]; n = 10, 61.1 [5.8] years of age) completed 6 weeks of high intensity interview training (HITT). Two way ANOVA suggested no group (SED, LEX) × time (pre, post) interaction on myostatin concentration (p = 0.649), nor a main effect of time (p = 0.757), however there was a trend towards increased myostatin in the LEX group relative to SED (p = 0.083). Discussion: Loss of muscle mass and function occurs at a predictable rate from ~30 years of age, however the rate of loss differs between active and inactive populations. Here we demonstrate that total circulating myostatin decreases as age increases, and differs significantly between males and females. Total circulating myostatin negatively correlates with increasing age, however alterations in myostatin do not appear after short term training interventions. Longer term activity may alter myostatin, thus our next work will follow up experiment 2 with a 3 year longitudinal analysis

    Investigation of the cardiac depressant effect of Caralluma tuberculate N.E.Br on isolated rabbit heart

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    Purpose: To investigate the histopathological and cardiac depressant effect of the aqueous methanol extract of Caralluma tuberculata N.E. Br (AMECT) (family: Asclepiadaceae)’ and to determine if there is a scientific basis for its cardiovascular diseases-related folkloric use. Methods: The effect of AMECT in different concentrations ranging from 0.00001 to 1.0 mg/mL were evaluated in isolated perfused rabbit heart to assess their effect on the force of contraction and heart rate using Langendorff’s apparatus. Atropine and adrenaline were used to identify the underlying mechanism of response produced by AMECT. The extract was studied for its possible mechanism in the absence and presence of atropine and adrenaline. In addition, sub-chronic toxicity and histopathological study of heart tissues in rats were assessed by administering 500 mg/kg of extract. Results: At all concentrations, AMECT produced significant (p < 0.001) negative ionotropic and negative chronotropic effects. The most significant effect was observed at 0.001 mg/mL and higher concentrations hence 0.001 mg/mL was selected for further studies. Pre-incubation with atropine did not significantly inhibit the effects of AMECT. However, AMECT significantly (p < 0.01) blocked the cardiac stimulant effect of adrenaline. In the histopathological studies, AMECT did not produce any significant cellular changes or signs of toxicity in the sub-chronic toxicity study. Conclusion: The cardiac-depressant responses of AMECT may involve the ÎČ-adrenergic receptors in the myocardium of isolated rabbit heart thus confirming the rationale for its use in ethnomedicine for cardiac diseases

    Circulating myostatin is reduced with aging in humans but not altered by short-term, high intensity training

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    Ageing involves a loss of muscle mass and function. The rate of decline is associated with negative health outcomes and increased mortality (1). Muscle atrophy is observed at a predictable rate from 30 years of age (2), however maintenance of function is seen in masters athletes > 60 years of age (3). Myostatin acts as a negative regulator of muscle mass (4) and underlies hypertrophy with chronic resistance training (5) and atrophy in chronic conditions (4). Experiment 1: Declared healthy participants (n = 83, 18 - 75 years of age, 36 male, 47 female) were recruited. Body composition, metabolic rate, grip strength and 6-minute walk test were recorded. Venous blood was collected and total myostatin concentration (herein referred to as myostatin) quantified by enzyme-linked immunosorbent assay. Total myostatin was lower in females compared with males (2176.1 [135.3] vs. 2788.7 [180.2] pg.mL-1 [p = 0.007]). Stepwise regression observed that myostatin concentration is best predicted firstly by gender, then by age (r = 0.399, p = 0.02), and was not further improved by the addition of measures of metabolism, muscle mass or function. Experimental 2: A cohort of aged sedentary (SED) males (n = 14; 63.9 [5.6] years of age) and masters athletes (lifelong exerciser [LEX]; n = 10, 61.1 [5.8] years of age) completed 6 weeks of high intensity interview training (HITT). Two way ANOVA suggested no group (SED, LEX) × time (pre, post) interaction on myostatin concentration (p = 0.649), nor a main effect of time (p = 0.757), however there was a trend towards increased myostatin in the LEX group relative to SED (p = 0.083). Discussion: Loss of muscle mass and function occurs at a predictable rate from ~30 years of age, however the rate of loss differs between active and inactive populations. Here we demonstrate that total circulating myostatin decreases as age increases, and differs significantly between males and females. Total circulating myostatin negatively correlates with increasing age, however alterations in myostatin do not appear after short term training interventions. Longer term activity may alter myostatin, thus our next work will follow up experiment 2 with a 3 year longitudinal analysis

    Clinical Utility of Amplification Refractory Mutation System-Based PCR and Mutation-Specific PCR for Precise and Rapid Genotyping of Angiotensin-Converting Enzyme 1 (ACE1-rs4646996 D>I) and Angiotensin-Converting Enzyme 2 (ACE2-rs4240157T>C) Gene Variations in Coronary Artery Disease and Their Strong Association with Its Disease Susceptibility and Progression

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    Background: Experimental clinical and research studies demonstrated that the renin–angiotensin system (RAS) affects the pathogenesis of atherosclerosis and the prognosis of coronary heart disease (CHD). The results show that ACE2 (angiotensin I-converting enzyme 2) might act as a protective protein for cardiovascular diseases; however, only a few studies in human populations have been carried out. The aim of this study was to develop, optimize, and validate a direct T-ARMS-based PCR assay for the precise and rapid genotyping of ACE1-rs4646996 D>I and ACE2-rs4240157T>C and study their association with coronary artery disease susceptibility and progression. Methodology: This study included 149 consecutive coronary artery disease patients and 150 healthy controls. We utilized T-ARMS for the precise and rapid genotyping of ACE2-rs4240157; rs4646994. Results: Our results indicated that the ACE1-rs4646996 D>I genotypes observed between CAD cases and controls were statistically significant (p < 0.008) and, similarly, the ACE2-rs4240157T>C genotypes observed were significant (p < 0.0001). Moreover, the frequency of the D allele (ACE1-D>I) and C allele (ACE2-rs4240157T>C) was found to be higher among CAD patients than the HC. Our results indicated that in the codominant model, the ACE2-ID genotype was strongly associated with increased CAD susceptibility in a codominant model with an OR of 2.37, (95%) CI = (1.023–5.504), and p < 0.04. Similarly, the ACE2-DD genotype was strongly associated with an increased CAD susceptibility with an OR of 3.48, (95%) CI = (1.49 to 8.117), and p < 0.003. Similarly, in allelic comparison, the D allele was strongly associated with CAD susceptibility with an OR of 1.59, (95%) CI = (1.12–2.24), and p < 0.003. Our results revealed that there was a significant correlation between ACE2-I/D genotypes and hypertension, T2D, and obesity (p < 0.05). The results of ACE2 rs4240157 genotyping indicated a strong association in the codominant model with an increased CAD susceptibility with an OR of 3.62, (95%) CI = (2.027 to 6.481), and p < 0.0001. Similarly, in a dominant inheritance model, a strong association is observed between the ACE2 rs4240157 (CT+CC) genotype with an OR of 6.34, (95%) CI = (3.741 to 10.749), and p < 0.0001. In allelic comparison, the T allele was strongly associated with CAD susceptibility with an OR of 5.56, (95% CI = (3.56 to 7.17), and p < 0.0001. Similarly, our results revealed that there was a significant association of the ACE2-rs4240157T>C genotypes with Triglycerides (mg/dL), HDL-C (mg/dL), total Cholesterol (mg/dL), and C-reactive protein (mg/L) in CAD. Conclusion: It was indicated that the ARMS technique and MS-PCR assay proved to be fast, accurate, and reliable for ACE2-rs4240157T>C and ACE1-rs4646996 D>I, respectively, and can be used as a potential molecular tool in the diagnosis of genetic diseases in undeveloped and developing countries—where there might be a shortage of medical resources and supplies. ACE1-I>D genotypes were strongly associated with T2D, hypertension, and obesity (p < 0.002). Besides the ACE2-rs4240157 CT heterozygosity genotype, the T allele was strongly associated with CAD susceptibility. Future longitudinal studies in different ethnic populations with larger sample sizes are recommended to validate these finding

    Vasorelaxant and Antihypertensive Effects of Bergenin on Isolated Rat Aorta and High Salt-Induced Hypertensive Rats

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    Bergenin is a phenolic glycoside that has been reported to be present in some medicinal plants which are traditionally used for their antihypertensive actions. So, bergenin was investigated for antihypertensive and vasorelaxant experiments in a rat model. Bergenin produced a significant fall in the mean arterial pressure (MAP) of rats. To explore the involvement of NO and muscarinic receptors, rats were pretreated with L-NAME and atropine in-vivo. The L-NAME did not change significantly the effect of bergenin on MAP excluding the involvement of NO. Unlike the L-NAME, atropine pretreatment reduced the effect of bergenin on MAP, indicating the role of muscarinic receptors. In in-vitro study, the bergenin produced endothelium-dependent (at lower concentrations) and independent (at higher concentrations) vasorelaxation, which was attenuated significantly in the presence of atropine and indomethacin but not with L-NAME. While a partial response was observed against K+-induced contractions. This was further confirmed when bergenin partly shifted the CaCl2-CRCs toward right. Bergenin also suppressed the PE peak formation, indicating the antagonist effect against the release of Ca2+. Moreover, the bergenin-induced vasorelaxant response was not markedly attenuated with TEA, while significantly ablated with 4-AP and BaCl2. In conclusion, the antihypertensive effects of bergenin are due to Ca2+ channel blockade, K+ channels activation, and muscarinic receptor-linked vasodilation

    Genetic Determinants of Cardiovascular Disease: The Endothelial Nitric Oxide Synthase 3 (eNOS3), KrĂŒppel-Like Factor-14 (KLF-14), Methylenetetrahydrofolate Reductase (MTHFR), MiRNAs27a and Their Association with the Predisposition and Susceptibility to Coronary Artery Disease

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    Coronary artery disease (CAD) is an important cause of death worldwide. CAD is caused by genetic and other factors including hypertension, hyperlipidemia, obesity, stress, unhealthy diet, physical inactively, smoking and Type 2 diabetes (T2D). The genome wide association studies (GWASs) have revealed the association of many loci with risk to diseases such as cancers, T2D and CAD. Nitric oxide (NO) is a potent vasodilator and is required for normal vascular health. It is produced in the endothelial cells in a reaction catalyzed by the endothelial NO synthase (eNOS). Methylenetetrahydrofolate reductase (MTHFR) is a very important enzyme involved in metabolism of folate and homocysteine, and its reduced function leads to cardiovascular disease. The KrĂŒppel-like factor-14 (KLF-14) is an important transcriptional regulator that has been implicated in metabolic syndrome. MicroRNA (MiRNAs) are short non-coding RNAs that regulate the gene expression of proteins involved in important physiological processes including cell cycle and metabolism. In the present study, we have investigated the potential impact of germline pathogenic variants of endothelial eNOS, KLF-14, MTHFR, MiRNA-27a and their association with risk to CAD in the Saudi population. Methods: Amplification Refractory Mutation System (ARMS) PCR was used to detect MTHFR, KLF-14, miRNA-27a and eNOS3 genotyping in CAD patients and healthy controls. About 125 CAD cases and 125 controls were enrolled in this study and statistical associations were calculated including p-value, risk ratio (RR), and odds ratio (OD). Results: There were statistically significant differences (p T, KLF-14 rs972283 G>A, miRNAs27a rs895819 A>G and eNOS3 rs1799983 G>T between CAD patients and controls. In addition, our results indicated that the MTHFR-TT genotype was associated with increased CAD susceptibility with an OR 2.75 (95%) and p p p = 0.016. Our results also indicated that eNOS3 -GT genotype is associated with CAD susceptibility with an OR = 2.65, and p T, KLF14 rs972283 G>A, miRNAs27a A>G, and eNOS3 rs1799983 G>T genotypes were associated with CAD susceptibility (p < 0.05). These findings require verification in future large-scale population based studies before these loci are used for the prediction and identification of individuals at risk to CAD. Weight control, physical activity, and smoking cessation are very influential recommendations given by clinicians to the at risk individuals to reduce or delay the development of CAD
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