ABSTRACT
Objective: To explore the possible anti-atherosclerotic mechanisms of glucose co-transporter-2 inhibitor canagliflozin. Methods: ApoE-/-mice fed on Western diet were randomly assigned into the model group (n=10) and the canagliflozin group (n=10). C57BL/6J mice fed on normal diet were chosen as the control group (n=10). Mice in the canagliflozin group were gavaged with canagliflozin for 14 weeks. The presence and severity of atherosclerosis were evaluated with HE and oil red O stainings in aortic root section slices. PCR assay was performed to determine the mRNA expression levels of nitric oxide synthase. Hepatic transcriptome analysis and hepatic amino acid detection were conducted using RNA-seq and targeted LC-MS, respectively. Results: HE staining and oil red O staining of the aortic root showed that AS models were successfully established in ApoE-/-mice fed on Western diet for 14 weeks. Canagliflozin alleviated the severity of atherosclerosis in pathology. Hepatic transcriptome analysis indicated that canagliflozin impacted on amino acid metabolism, especially arginine synthesis in ApoE-/-mice. Targeted metabolomics analysis of amino acids showed that canagliflozin reduced hepatic levels of L-serine, L-aspartic acid, tyrosine, L-hydroxyproline, and L-citrulline, but raised the hepatic level of L-arginine. Compared to the model group, the canagliflozin group exhibited higher serum arginine and nitric oxide levels as well as elevated nitric oxide mRNA expression in aortic tissues (P<0.05). Conclusion: Canagliflozin regulated the amino acid metabolism, reduced the levels of glucogenic amino acids,and promoted the synthesis of arginine in atherosclerotic mice.
Subject(s)
Mice , Animals , Canagliflozin/therapeutic use , Nitric Oxide , Mice, Knockout , Mice, Inbred C57BL , Atherosclerosis/drug therapy , Arginine , Amino Acids , Apolipoproteins E , RNA, Messenger , Plaque, Atherosclerotic , Azo CompoundsABSTRACT
Objective: To explore the possible anti-atherosclerotic mechanisms of glucose co-transporter-2 inhibitor canagliflozin. Methods: ApoE-/-mice fed on Western diet were randomly assigned into the model group (n=10) and the canagliflozin group (n=10). C57BL/6J mice fed on normal diet were chosen as the control group (n=10). Mice in the canagliflozin group were gavaged with canagliflozin for 14 weeks. The presence and severity of atherosclerosis were evaluated with HE and oil red O stainings in aortic root section slices. PCR assay was performed to determine the mRNA expression levels of nitric oxide synthase. Hepatic transcriptome analysis and hepatic amino acid detection were conducted using RNA-seq and targeted LC-MS, respectively. Results: HE staining and oil red O staining of the aortic root showed that AS models were successfully established in ApoE-/-mice fed on Western diet for 14 weeks. Canagliflozin alleviated the severity of atherosclerosis in pathology. Hepatic transcriptome analysis indicated that canagliflozin impacted on amino acid metabolism, especially arginine synthesis in ApoE-/-mice. Targeted metabolomics analysis of amino acids showed that canagliflozin reduced hepatic levels of L-serine, L-aspartic acid, tyrosine, L-hydroxyproline, and L-citrulline, but raised the hepatic level of L-arginine. Compared to the model group, the canagliflozin group exhibited higher serum arginine and nitric oxide levels as well as elevated nitric oxide mRNA expression in aortic tissues (P<0.05). Conclusion: Canagliflozin regulated the amino acid metabolism, reduced the levels of glucogenic amino acids,and promoted the synthesis of arginine in atherosclerotic mice.
Subject(s)
Mice , Animals , Canagliflozin/therapeutic use , Nitric Oxide , Mice, Knockout , Mice, Inbred C57BL , Atherosclerosis/drug therapy , Arginine , Amino Acids , Apolipoproteins E , RNA, Messenger , Plaque, Atherosclerotic , Azo CompoundsABSTRACT
Objective: To explore the relationship between lipoprotein(a) [Lp(a)] and chronic cardio-renal syndrome (CRS) in elderly patients. Methods: Chronic heart failure (CHF) patients age ≥ 65 years old, who hospitalized in the department of Cardiology of Hebei General Hospital from December 2017 to October 2019, were included in this study. According to the estimate glomerular filtration rate (eGFR) level, patients were divided into CRS group (eGFR<60 ml·min-1·1.73 m-2) and CHF group (eGFR ≥60 ml·min-1·1.73 m-2). The blood index and basic disease information were collected and compared. Left ventricular ejection fraction (LVEF) were measured by echocardiography. The correlation between clinical indicators and cardio-renal function (LVEF and eGFR) was assessed. The multivariate logistic regression analysis was used to evaluate the related risk factors of CRS in elderly patients; subgroup logistic regression analysis was performed according to the basic disease of patients to assess the relationship between Lp(a) and CRS. Results: A total of 172 elderly patients (85 males (49.4%), aged 79 (71, 84) years) were finally enrolled. Among them, 88 cases (51.2%) were in CRS group and 84 cases (48.8%) were in CHF group. Age (80 (74, 84) years old vs. 74 (70, 82) years old) and LP (a) levels (222.0 (112.0, 445.3) mg/L vs. 155.0 (97.0, 348.7) mg/L) were significantly higher in the CRS group than in the CHF group (P<0.05). Lp(a) levels were negatively correlated with LVEF (r=-0.155, P=0.043) and eGFR (r=-0.220, P=0.004) in total cohort. In the subgroup analysis of patients with 2 high-incidence basic diseases (coronary heart disease and hypertension), Lp(a) was negatively correlated with LVEF (r=-0.250, P=0.007) in the coronary heart disease group, and negatively correlated with eGFR (r=-0.233, P=0.013) in the hypertension group. Multivariate logistic regression analysis showed that age (OR = 1.069, 95%CI: 1.017-1.124, P= 0.009) and Lp(a) (OR = 3.719, 95%CI: 1.339-10.326, P = 0.012) were independent correlates of CRS. The results of logistic regression analysis showed that Lp(a) was an independent correlative factor of CRS in the subgroups of coronary heart disease (OR=3.207, 95%CI: 1.129-9.108, P=0.029) and hypertension (OR=3.054, 95%CI: 1.086-8.587, P=0.034). Conclusion: Serum Lp(a) level is independently related with CRS in elderly patients.
Subject(s)
Aged , Aged, 80 and over , Humans , Male , Cardio-Renal Syndrome , Heart Failure , Lipoprotein(a) , Prognosis , Stroke Volume , Ventricular Function, LeftABSTRACT
Objective To study the effect of age and sex on circadian rhythms of renin-angiotensin system(RAS) .Methods 96 SPRD rats were divided into three groups.The levels of renin(Ren)activity,angiotensin Ⅱ(Ang Ⅱ)and angiotensin-converting-enzyme(ACE)in plasma or serum were respectively determined.Results The plasma or serum levels of renin,ACE,and angiotensin-Ⅱ in adult male group(D group)were significantly increased in comparison with elderly male group(M group)and elderly female group(F group).There were not significantly different between F group and M group in the levels of Ren activity,AngⅡ and ACE.The three substances presented typical circadian rhythms in three groups(P