Effect of short-chain acyl-CoA dehydrogenase on cardiac hypertrophy induced by hypertension or exercise training

AIM: To investigate the differential expression of short-chain acyl-CoA dehydrogenase (SCAD) in cardiac hypertrophy induced by hypertension or exercise training. METHODS: Spontaneously hypertensive rats (SHR) were used as the model of pathological cardiac hypertrophy. The swim-trained rats were used as the model of physiological cardiac hypertrophy. The systolic pressure, cardiac hypertrophy parameters, echocardiogram parameters, free fatty acid in serum and cardiac muscle, and the expression and activity of SCAD in the left ventricle were measured. RESULTS: Compared with the control rats, trained rats developed an athletic heart, of which cardiac function was enhanced, whereas SHR developed hypertensive cardiac hypertrophy, of which cardiac function was deteriorated. Compared with the control rats, the ratios of left ventricular weight to body weight were both increased in trained rats and SHR, showing that the degrees of cardiac hypertrophy were similar in the 2 models. Compared with the control rats, the decrease of free fatty acid both in serum and myocardium indicated that the fatty acid utilization was increased in the left ventricle of trained rats. Meanwhile, the expression and activity of SCAD in the left ventricle of trained rats were increased. However, free fatty acid both in serum and myocardium were increased, indicating that the fatty acid utilization was decreased in the left ventricle of SHR. Furthermore, SHR had the decreased expression and activity of SCAD in the left ventricle. CONCLUSION: The changes of SCAD are different in cardiac hypertrophy induced by hypertension and exercise training, indicating that SCAD may be used as a molecular marker of physiological and pathological cardiac hypertrophy, and a potential therapeutic target of pathological cardiac hypertrophy.     

Effects of short-chain acyl-CoA dehydrogenase on hypertensive vascular remodeling

AIM: To investigate the changes of short-chain acyl-CoA dehydrogenase (SCAD) in hypertensive vascular remodeling and to explore the relationship between SCAD and vascular remodeling in hypertension.METHODS: The spontaneously hypertensive rats (SHR; 24 weeks old) and Wistar rats (24 weeks old) were used as experimental control groups. The SHR and Wistar rats of 16 weeks old were trained by swimming as experimental groups. The systolic pressure was measured periodically. The thickness of vascular wall and the diameter of the vascular lumen were measured. The contents of ROS and ATP, the enzyme activity of SCAD, and the expression of SCAD at mRNA and protein levels in the aorta were determined. The free fatty acid in the serum and aorta was also measured.RESULTS: Compared with Wistar group, the diameter of vascular lumen decreased in SHR group. The thickness of vascular wall, the ratio of vascular wall and the diameter of vascular lumen, and the blood pressure in SHR group were increased significantly (P<0.05). Compared with SHR group, the diameter of vascular lumen increased in SHR+swim group. The thickness of vascular wall, the ratio of vascular wall and the diameter of vascular lumen, and the blood pressure in SHR+swim group were decreased significantly. Compared with control group, the expression of SCAD at mRNA and protein levels, the enzyme activity of SCAD, and the content of ATP were decreased in SHR group. However, the free fatty acid in the serum and aorta, and the content of ROS in the aorta were increased in SHR group. The expression of SCAD at mRNA and protein levels, the enzyme activity of SCAD, the content of ATP were increased in Wistar+swim group and SHR+swim group. However, the free fatty acid in serum and aorta, and the content of ROS in the aorta were decreased in Wistar+swim group and SHR+swim group.CONCLUSION: Decrease in SCAD expression may be associated with hypertensive vascular remodeling. Swimming training can reverse hypertensive vascular remodeling by increasing the expression of SCAD in the aorta.     

Effects of short-chain acyl-CoA dehydrogenase on collagen expression and proliferation of rat cardiac fibroblasts

AIM: To investigate the effect of short-chain acyl-CoA dehydrogenase (SCAD) on collagen expression and proliferation of rat cardiac fibroblasts and to explore the relationship between SCAD and cardiac fibrosis. METHODS: The model of proliferation and collagen expression of rat cardiac fibroblasts induced by angiotensin II was established. After treatment with siRNA-1186, the expression of SCAD at mRNA and protein levels, fatty acids beta oxidation rate, ATP, the enzyme activity of SCAD and free fatty acids in the rat cardiac fibroblasts were determined. RESULTS: The mRNA and protein expression of SCAD was decreased in the rat cardiac fibroblasts induced by angiotensin II compared with the control cells, and the expression of collagen I and collagen III was significantly upregulated. Compared with negative control group, SCAD expression and activity, fatty acid beta-oxidation rate and ATP significantly decreased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the rat cardiac fibroblasts, and the expression of collagen I and collagen III was significantly up-regulated. CONCLUSION: The expression and synthesis disorder of collagen may be triggered by down-regulation of SCAD. SCAD may be a promising therapeutic target for myocardial fibrosis.     

Effect of atorvastatin on ventricular remodeling in spontaneous hypertension rats

AIM：To explore the effect of atorvastatin on cardiac remodeling in spontaneous hypertension rats (SHR).METHODS：Twelve spontaneous hypertension rats were divided randomly into two groups：group of atorvastatin (atorvastatin 50 mg·kg^-1·d^-1) and group of SHR (0.5% mucilage of arabic gum,10 mL·kg^-1·d^-1).Additionally,six male Wistar-Kyoto rats (0.5% mucilage of arabic gum,10 mL·kg^-1·d^-1) were selected as control group.Systolic blood pressure was assessed with the tail-cuff method.After six weeks,entire heart,and left ventricle were weighed.The left ventricular weight index was calculated and myocardial hydroxyproline and collagen protein concentration were measured.The serum high sensitivity CRP (hs-CRP) was measured by nephelometry.The localization of vascular cell adhesion molecule (VCAM) in myocardium was investigated by immunohistochemistry assays.The level of NF-κB mRNA expression was detected with in situ hybridization.Ultrastructure in cardiac muscle was also observed under transmission electron microscope.RESULTS：The expression of myocardial VCAM and NF-κB in SHR group was stronger than that in WHY group.Compared with SHR group,entire heart weight,left ventricular weight,left ventricular weight index,serum hs-CRP,myocardial hydroxyproline and collagen protein concentration was decreased,the expression of myocardial VCAM and NF-κB in SHR group was weaker than that in atorvastatin treatment group.The myocardial pathological change such as incomplete karyotheca in cardiac muscle cells,no clear of transverse striation and the mess in myofibril alignment,and hyperplasy in interstitial collagen fibre were observed in SHR group and these changes were improved in atorvastatin treatment group.CONCLUSION：The cardiac remodeling in SHR is improved by atorvastatin.The molecular mechanism may be related to its down-regulating the expression of VCAM protein and NF-κB and inhibiting myocardial chronic inflammation.     

Role of carvedilol on energy metabolic reversion and remodeling of pressure overload-induced left ventricular hypertrophy in rats

AIM: To study changes of medium chain acyl-CoA dehydrogenase (MCAD), muscle carnitine palmitoyltransferase I (M-CPT-I) and colligin mRNA/protein expression, to elucidate molecular mechanism of the recapitulation of fetal energy metabolism and ventricular remodeling and the effects of carvedilol during the development of pressure overload-induced left ventricular hypertrophy in rats. METHODS: Male Wistar rats of hypertrophy induced by constriction of abdominal aorta （CAA） were randomized into 2 groups (n=12, each group): 4-week group (CAA4 weeks group) and 12-week carvedilol intervention group (CAR group). Additional rats (n=12) underwent abdominal cavity incision without ligation to serve as age-matched sham operated controls (SH). Hemodynamics, ventricular remodeling parameters and free fatty acid （FFA） both in blood serum and myocardium were measured. RT-PCR analysis of the expression of mRNA of M-CPT-I, MCAD and collagen binding protein (colligin) were investigated. The protein expression of colligin was analyzed by Western blotting in the experimental animals and sham operation.RESULTS: LVM/BW and MAP in CAA group were increased more significantly than in sham group. There were progressive increases in FAA both in blood serum and myocardium in CAA group than in sham group, accompanied with downregulation of gene expressions of M-CPT-I and MCAD and colligin mRNA/ protein upregulation in LV in CAA group, while changes of all of these parameters in CAR group were attenuated.CONCLUSIONS: (1) The down-regulated expression of cardiac FAO enzyme genes (M-CPT-I and MCAD) in the hypertrophied heart may be responsible for “the recapitulation of fetal energy metabolism” during the development of pressure overload-induced left ventricular hypertrophy in rats. (2) Carvedilol attenuates the reversion of the metabolic gene expression back towards fetal type. (3) Carvedilol is effective in regressing the left ventricular remodeling by inhibiting colligin protein expression. A molecular mechanism by which carvedilol may confer cardioprotective effects in heart failure may be, in part, via preserving of the adult metabolic gene regulation and regressing left ventricular remodeling.     

Alterations in gene expression of sarcoplasmic reticulum Ca2+-ATPase and phospholamban detected by RNA array in spontaneously hypertensive rats

AIM: To explore the relationship between the alteration in gene expression of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) and phospholamban (PLB) in spontaneously hypertensive rats (SHR). METHODS: 294 samples of total RNA were obtained from the tissue of ventriculum , aortic smooth muscle, liver and kidney in SHR and normotensive rats (WKY). RNA array was used to determine the mRNA levels of SERCA and PLB. RESULTS: Compared with age-matched WKY rats, the systolic blood pressure increased higher in 6-week-old SHR (P<0.01). The cardiosomatic ratio was significantly higher in 10-week-old SHR (P<0.01), in cardiac sarcoplasmic reticulum, the mRNA levels of SERCA were significantly increased from 4 weeks (P<0.05 or P<0.01). In the aortic sarcoplasmic reticulum, the mRNA levels of SERCA were significantly increased from 4 weeks to 12 weeks (P<0.05 or P<0.01). There was no significant change in the expression of PLB between the two groups. The ratio of cardiac SERCA and PLB was significantly increased since 6-week-old (P<0.05 or P＜0.05)in SHR. The ratio of aortic SERCA and PLB in SHR was significantly increased since 4-week-old (P<0.05 or P<0.01) vs WKY. CONCLUSION: Our results provided the evidence that the abnormalities of intracellular Ca²⁺ hemostasis in SHR represent the progressive nature of essential hypertension.     

Relationship of microRNA-133a and TGF-β1 protein in myocardial tissues of spontaneously hypertensive rats

AIM：To observe the changes of microRNA-133a and transforming growth factor β1 (TGF-β1) protein in the myocardium of spontaneously hypertensive rats (SHR). METHODS：Male SHR (18 weeks old, n=12) and male Wistar-Kyoto rats (WKY, 18 weeks old, n=12) served as SHR group and control group, respectively. Caudal arterial blood pressure was detected by a noninvasive blood pressure measurement and analysis system. Myocardial collagen volume fraction (CVF) and perivascular collagen area ratio (PVCA) were determined by Masson staining. The level of miR-133a in the heart was detected by real-time quantitative PCR. The protein level of TGF-β1 in the heart was also analyzed by the methods of immunohistochemisty and Western blotting. RESULTS：Compared with control group, systolic and diastolic blood pressure, CVF and PVCA significantly increased, the expression of TGF-β1 protein was significantly up-regulated, and the level of miR-133a was significantly reduced in SHR group. In SHR group, the expression of miR-133a was decreased to (23.9±4.6)% in control group. A negative correlation between the levels of miR-133a and TGF-β1 protein in SHR group was observed (r=-0.791, P<0.01). CONCLUSION：The level of miR-133a is down-regulated along with the up-regulation of TGF-β1 protein expression and collagen synthesis in the myocardial tissues of SHR. miR-133a and TGF-β1 may be involved in myocardial fibrosis in SHR.     

Relationship between the intracellular calcium concentration changes and left ventricular hypertrophy and function in the spontaneously hypertensive rats

AIM:To elucidate the relationship between the intracellular calcium concentration changes and left ventricular hypertrophy and function in the spontaneously hypertensive rats (SHR).METHODS:Intracellular free calcium concentrations were measured by Fura 2 methodology and left ventricular function quantitated by cardiac catheterization in 20 SHR aged 10, 22, and 34 weeks and 20 age-matched Wistar-kyoto (WKY) rats.RESULTS:(1) The systolic blood pressure(SBP), intracellular calcium concentrations and left ventricular mass / body weight index (LVM/BW) were significantly higher in all three age groups of SHR than the corresponding groups of WKY; (2) Compared with age-matched WKY groups, the peak left ventricular pressure descending rate(-dp／dt_max) decreased while left ventricular relaxation time constant (τ)increased significantly in SHR aged 22 and 34 weeks. The peak left ventricular pressure ascending rate(dp／dt_max) and the left ventricular contractility index were significantly increased only in the 34 weeks SHR; (3) Intracellular calcium concentrations showed a positive correlation with LVM/BW,SBP,-dp／dt_max and τ(r=0.47-0.83,P<0.01)and a negative correlation with dp／dt_max and the left ventricular contractility index (r=-0.46,P<0.05 and r=-0.81, P<0.01).CONCLUSION:Intracellular calcium overload is one of the potential mechanisms in the induction of left ventricular hypertrophy as well as of systolic and diastolic dysfunction.     

Activated AMPK attenuates cardiac hypertrophy in rats through increasing myocardial fatty acid oxidation

AIM: To investigate the antihypertrophic function of adenosine monophosphate-activated protein kinase(AMPK) and its effects on myocardial fatty acid oxidation.METHODS: The model of cardiac hypertrophy was produced by banding abdominal aorta (transaortic constriction, TAC) in male Sprague-Dawley rats. 5-aminoimidazole-4-carboxamide ribonucleoside(AICAR), a pharmacological activator of AMPK, was injected subcutaneously (0.5 mg·kg-1·d-1) 24 hours after operation and continued till 7 weeks after operation. Echocardiographic and ventricular remodeling parameters, free fatty acid concentration in blood serum and myocardium, and expression of peroxisome proliferator-activated receptor(PPARα) and carnitine palmityl transferase(CPT-I) mRNA were investigated after treatment of AICAR or vehicle for 7 weeks. RESULTS: Compared with control group, treatment of rats subjected to TAC with AICAR significantly increased the mRNA expression of PPARα and CPT-I and subsequently decreased free fatty acid concentration in blood and myocardium, improved echocardiographic characteristics, and reduced the increases in the heart weight/body weight ratio and myocyte diameter.CONCLUSION: Pharmacological activation of AMPK may attenuate cardiac hypertrophy through increasing myocardial fatty acid oxidation.     

Effect of atorvastatin on HMG-CoA reductase expression in spontaneously hypertensive rats

AIM: To evaluate the effect of atorvastatin on HMG-CoA reductase (HMGR) expression level in spontaneously hypertensive rats (SHR). METHODS: Twelve eight-week-old SHR was randomized into distilled water group (SHR_DW group, n=6) and atorvastatin-treated group (SHR_ATV group, n=6). The age-matched Wistar-Kyoto rats (WKY) were used as control (WKY group, n=6). RT-PCR and Western blotting were used to detect HMGR mRNA and protein expression levels, respectively. Meanwhile, systolic blood pressure (SBP) and serum lipid levels were examined. RESULTS: Ten weeks a treatment, SBP in SHR_ATV group was markedly decreased compared with before treatment and SHR_DW group (P<0.05). The levels of TC, TG, LDL-C and HDL-C in SHR_ATV group were also markedly lower than those in SHR_DW group and WKYgroup (P<0.05). 10 weeks later, HMGR mRNA levels decreased markedly in SHR_ATV group compared to WKY group and SHR_DW group (P<0.05). The similar results were found in HMGR protein expression levels. CONCLUSIONS: Atorvastatin downregulates mRNA and protein expression levels of HMGR in SHR, which not only decreases the serum lipids levels, but also impacts blood pressure to a certain extent.     

Effects of ERK1/2/PPARα/SCAD signal pathways on physiological cardiac hypertrophy and pathological cardiac hypertrophy

AIM：To investigate the different effects of ERK1/2/PPARα/SCAD (short-chain acyl-CoA dehydrogenase) signal pathways on the cardiac hypertrophy induced by insulin-like growth factors 1 (IGF-1) or phenylephrine (PE). METHODS：The neonatal rat cardiomyocytes induced by IGF-1 were used as the model of physiological cardiac hypertrophy, and those induced by PE were used as the model of pathological cardiac hypertrophy. The surface area of the cardiomyocytes, the expression of p-ERK1/2, PPARα and SCAD, the activity of SCAD and the content of free fatty acid in the cardiomyocytes were measured. RESULTS：Compared with the control cells, the surface area of the cardiomyocytes induced by IGF-1 and PE were both increased. Compared with the controls, the expression of SCAD and PPARα, and the activity of SCAD in the cardiomyocytes induced by IGF-1 were increased, while the expression of p-ERK1/2 was decreased. However, the cardiomyocytes treated with PE showed decreased expression of SCAD and PPARα, decreased activity of SCAD and increased expression of p-ERK1/2. Meanwhile, the decrease in free fatty acid in IGF-1-induced cardiomyocytes and the increase in PE-induced cardiomyocytes indicated that the fatty acid utilization was increased in the cardiomyocytes induced by IGF-1, but decreased in the cardiomyocytes induced by PE. CONCLUSION：The changes of p-ERK1/2, PPARα and SCAD in the cardiac hypertrophy induced by IGF-1 or PE indicate that the effects of ERK1/2/PPARα/SCAD signal pathways are different between physiological cardiac hypertrophy and pathological cardiac hypertrophy, and that SCAD may be a molecular marker of these 2 different cardiac hypertrophies and a potential therapeutic target for pathological cardiac hypertrophy.     

Effects of short-chain acyl-CoA dehydrogenase on cardiomyocyte apoptosis

AIM: To investigate the change of short-chain acyl-CoA dehydrogenase(SCAD) expression during cardiomyocyte apoptosis and to explore the relationship between SCAD and cardiomyocyte apoptosis.METHODS: The neonatal rat cardiomyocytes treated by tert-butyl hydroperoxide(tBHP) were used as the model of cardiomyocyte apoptosis. The cell viability, the expression of SCAD at mRNA and protein levels, the activity of SCAD and the content of free fatty acids were determined.RESULTS: The mRNA and protein expression of SCAD decreased in the cardiomyocyte apoptosis model. Compared with negative control group, SCAD expression and activity were both significantly decreased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the cardiomyocytes. Meanwhile, SCAD siRNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP.CONCLUSION: Down-regulation of SCAD may play an important role in primary cardiomyocyte apoptosis. Increase in the expression of SCAD may become an important part in intervening cardiomyocyte apoptosis.     

Up-regulation of miR-133a expression attenuates myocardial fibrosis in spontaneously hypertensive rats

AIM: To investigate the effect of up-regulated expression of microRNA-133a (miR-133a) on myocardial fibrosis in spontaneously hypertensive rats (SHR). METHODS: Wistar-Kyoto (WKY) rats with homologous normal blood pressure served as the normal control group. SHR were divided into SHR group, SHR+ adeno-associated virus (AAV) group and SHR+miR-133a-AAV group randomly. miR-133a carried by miR-133a-AAV was transfected into SHR heart by coronary perfusion. The rat tail artery pressure was monitored. The myocardial collagen deposition was observed by Masson staining. The expression of miR-133a in myocardial tissue was detected by real-time PCR. The protein levels of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were determined by immunohistochemistry and Western blot. RESULTS: Compared with the WKY rats, the tail artery pressure of the SHR increased significantly. The expression of miR-133a in heart decreased, and the expression levels of TGF-β1 and CTGF increased (P<0.05), and myocardial fibrosis occurred. After up-regulating the expression level of miR-133a in the heart of SHR, the myocardial fibrosis was significantly reduced, and the expression levels of TGF-β1 and CTGF decreased (P<0.05). CONCLUSION: Up-regulation of the miR-133a expression improves myocardial fibrosis induced by hypertension, which may be related to inhibiting the protein expression of TGF-β1 and CTGF in myocardium.     

Role of benazepril on extracellular signal-regulated kinase activity and expression of B-type natriuretic peptide in spontaneously hypertensive rats

AIM：To investigate the role of benazepril on extracellular signal-regulated kinase (ERK) activity and expression of B-type natriuretic peptide in spontaneously hypertension rat (SHR).METHODS：Wistar Kyoto rats were used as control group.Twenty one 14-week-age SHR were randomized into 3 groups,7 rats each：benazepril group (10 mg·kg-1·d-1);hydralazine group (10 mg·kg-1·d-1) and sham group.In each group drugs or equal volume of vehicle (0.5% carboxymethyl cellulose) were administered respectively for 10 weeks by gavage.The ratio of left ventricle weight to body weight （LVW/BW） was measured to reflect myocardial hypertrophy.The caudal arterial pressure was measured by tail-cuff.Protein expression of p-ERK in myocardial tissue was detected by Western blotting,BNP mRNA in myocardial tissue was examined by RT-PCR,and protein expression of plasma BNP was detected by ELISA.RESULTS：1.Benazepril and hydralazine lowered the blood pressure after 10 weeks treatment (P<0.01).2.The ratio of LVW/BW in SHR benazepril group was significantly lower than that in SHR hydralazine group and SHR sham group (P<0.01),and similar to that in WKY group (P>0.05).3.The protein expression of p-ERK in myocardial tissue in SHR benazepril group was significantly lower than that in SHR hydralazine group and SHR sham group (P<0.01),and similar to that in WKY group (P>0.05).There was no significant difference of p-ERK expression between SHR hydralazine group and SHR sham group (P>0.05).4.The levels of plasma BNP and BNP mRNA in myocardial tissue in SHR benazepril group were significantly lower than that in SHR hydralazine group and SHR sham group (P<0.01),and similar to that in WKY group (P>0.05).There was no significant difference of plasma BNP and BNP mRNA in myocardial tissue between SHR hydralazine group and SHR sham group (P>0.05).CONCLUSIONS：Benazepril inhibited ERK activation,resulting in regression of myocardial hypertrophy and accompanied by the reduction of BNP level.However,in spite of the effect of lowering blood pressure,hydralazine did not prevent or regress cardiac hypertrophy and did not decrease the level of p-ERK and BNP in SHR.BNP level might serve as a therapeutic index for reversal of myocardial hypertrophy.     

Regulation of AMPK/PPARα/SCAD signal pathway on cardiac hypertrophy

AIM：To study the effect of short-chain acyl-coenzyme A dehydrogenase (SCAD）on cardiac hypertrophy and to explore the role of adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor α (PPARα） signal pathway in the regulation of SCAD during the development of cardiac hypertrophy. METHODS：The optimal sequence of SCAD interference was chosen by Western blotting and real-time PCR. The cardiomyocytes were treated with fenofibrate (10 μmol/L) for 24 h and subsequently stimulated with the optimal sequence of SCAD interference. The changes of SCAD expression at mRNA and protein levels, the enzyme activity of SCAD, the cardiomyocyte surface area and free fatty acids were determined. Using real-time PCR for analyzing the markers of cardiac hypertrophy, the mRNA expression of atrial natriuretic factor (ANF） and brain natriuretic peptide (BNP) was detected to judge the development of cardiac hypertrophy. The cardiomyocytes were treated with fenofibrate (10 μmol/L) or AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 0.5 mmol/L) for 30 min and subsequently stimulated with phenylephrine (PE, 20 μmol/L) for 24 h. The changes of cardiomyocyte surface area, free fatty acids, and the expression of SCAD, PPARα and p-AMPKα (T172) at mRNA and protein levels were observed. RESULTS：The effect of optimal sequence siRNA-1186 and PE on the cardiomyocytes was the same. Compared with control group, the expression of ANF and BNP at mRNA level, the cardiomyocyte surface area and free fatty acids were increased obviously in siRNA-1186 group. After pretreated with fenofibrate (10 μmol/L), the expression of PPARα and SCAD, and the enzyme activity of SCAD were significantly increased, while the free fatty acids were decreased, indicating that fenofibrate prevented the development of cardiac hypertrophy induced by knockdown of SCAD. Compared with control group, the expression of SCAD, PPARα and p-AMPKα (T172) at mRNA and protein levels was significantly down-regulated, and the enzyme activity of SCAD was obviously decreased in PE group. Compared with PE group, the expression of SCAD, PPARα and p-AMPKα (T172) was significantly up-regulated, and the cardiomyocyte surface area and the content of free fatty acids were obviously decreased in the cardiomyocytes pretreated with fenofibrate or AICAR for 30 min. CONCLUSION：Down-regulation of SCAD is related to the cardiac hypertrophy and energy metabolism. AMPK/PPARα/SCAD signaling pathway may regulate cardiac hypertrophy directly.     

Effects of atorvastatin on myocardium expression of peroxisome proliferator-activated receptors in spontaneously hypertensive rats

AIM: To investigate the effects of atorvastatin on myocardium peroxisome proliferator-activated receptors (PPARs) expression, regression of left ventricular hypertrophy, and the possible mechanisms in spontaneously hypertensive rats (SHR). METHODS: 16 nine-week-old male spontaneously hypertensive rats were randomly divided into two groups: SHR received atorvastatin at dose of 30 mg·kg-1·d-1 by oral gavage once daily for 8 weeks (SHR-A, n=8), and SHR received vehicle (0.9% saline) as controls (SHR, n=8). Age-matched Wistar-kyoto rats received vehicle for 8 weeks were served as normaltensive controls (WKY, n=8). Systolic blood pressure was measured at the beginning, 2, 4 and 8 weeks of the experiment. At the end of the experiment, plasma lipid levels were measured. Left ventricular hypertrophy was accessed by pathological analysis. The expressions of PPARα and PPARγ were investigated by the method of Western blotting. RESULTS: There was not much difference of systolic blood pressure and plasma lipid levels between SHR-A and SHR group (P>0.05). Compared with SHR group, left ventricular weight mass index decreased significantly in SHR-A group (P<0.01). The myocardium PPARα and PPARγ expression increased significantly (P<0.01). CONCLUSION: Atorvastatin regresses left ventricular hypertrophy and increases myocardium PPARα and PPARγ expression in spontaneously hypertensive rats, which is independent of its lipid-lowering activity.     

Administration of magnolol postpones development of hypertension in juvenile spontaneous hypertensive rats

AIM:To investigate the effects of magnolol (MAG) on blood pressure and aortic vasodilatation to insulin in juvenile spontaneous hypertensive rats (SHR). METHODS:Four-week-old male SHR and age-matched normotensive Wistar-Kyoto (WKY) control rats were used. SHR and WKY rats were randomized into 2 groups and treated daily by gavage with vehicle (distilled water) or MAG (100 mg·kg-1·d-1). After 3 weeks of treatment, blood pressure, aortic vasorelaxation, fasting glucose and plasma insulin levels, the expressions of PPARγ and TRB3, and insulin-stimulated Akt/endothelial nitric oxide synthase (eNOS) activation were measured. In vitro, human umbilical vein endothelial cells (HUVECs) were cultured in the medium containing glucose (25 mmol/L) and palmitate (500 μmol/L). RESULTS:Treatment of young SHR with MAG for 3 weeks decreased blood pressure, improved insulin-induced aortic vasodilation, and Akt and eNOS activation , increased PPARγ expression and decreased TRB3 expression. In cultured HUVECs, MAG incubation increased PPARγ exprssion, decreased TRB3 expression, and elevated insulin-induced phosphorylated Akt and eNOS levels and NO production, which were reversed by PPARγ antagonist. CONCLUSION: Treatment of young SHR with MAG at the prehypertensive stage decreases blood pressure via improving vascular insulin resistance that is at least partly attributable to up-regulation of PPARγ, down-regulation of TRB3 and consequently activation of Akt and eNOS in blood vessel .     

Effects of atorvastatin on expression of cytochrome P450 hydroaylase in spontaneously hypertensive rats

AIM: To investigate the effects of atorvastatin on blood pressure and expression of cytochrome P450 hydroaylase (CYP) 4A1 in spontaneously hypertensive rats (SHR). METHODS: SHRs (n=18) were randomly divided into three groups: SHR control group, 50 mg atorvastatin (HATV) group and 10 mg (LATV) group. Six male Wistar-Kyoto rats were selected as normal control group (WKY group). All rats were given vehicle once a day by gavage for 10 weeks. Systolic blood pressure (SBP) was measured before and after treatment every 2 weeks. The expressions of CYP 4A1 mRNA and protein in heart, liver, kidney, and aorta were detected by RT-PCR and Western blotting analysis, respectively. Plasma lipids were also measured.RESULTS: SBP in all SHR groups was much higher than that in WKY group before experiment (P<0.01). Compared with SHR control group, SBP significantly decreased in HATV group at 6, 8, 10 weeks and in LATV group merely at 10 weeks (P<0.01 or P<0.05). The expressions of CYP 4A1 mRNA and protein in heart, liver, kidney and aorta tissues of SHR control group were significantly higher than those in WKY group (P<0.01 or P<0.05). After 10 weeks, the levels of CYP 4A1 mRNA, protein and plasma lipids in HATV and LATV groups were markedly lower than those in SHR control group (P<0.01 or P<0.05).CONCLUSION: Atorvastatin down-regulates the expressions of CYP 4A1 mRNA and protein in SHR, which may be the mechanism of the favorable effects of statins on regulation of hypertension.     

Expression of ERK and MKP-1 in vascular smooth muscle of spontaneously hypertensive rats with different ages

AIM: To investigate the expression of mitogen- activated protein kinase and mitogen-activated protein kinase phosphatase-1 in thoracic aorta smooth muscles of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) with different ages and the relationship between those and hypertension. METHODS: The caudal arterial pressure was measured by tail-cuff. Protein expression of p-ERK was detected by Western blotting, and MKP-1 mRNA in thoracic aorta smooth muscle was examined by RT-PCR. RESULTS: (1) The blood pressure of SHR was obviously higher than that of age-matched WKY (P<0.01), elevated with age (P<0.05) and became stable from 14-week-old. (2) The expression of p-ERK and MKP-1 in SHR was higher than that in WKY in 5-week-old rats, and the expression of p-ERK increased with age, while the expression of MKP-1 decreased with age (P<0.05). CONCLUSION: MKP-1 may play an important role in the development of hypertension in SHR. The decrease in the expression of MKP-1 that resulted in the activation of MAPK may induce vascular smooth muscle proliferation and hypertrophy.