Effect of fluvastatin on left ventricular remodeling and caspase-3 expression after myocardial infarction in rats

AIM: To observe the effect of fluvastatin (FV) on left ventricular remodeling and expression of caspase-3 after myocardial infarction (MI) in rats. METHODS: Rats were divided into 4 groups: group Ⅰ (sham), group Ⅱ (sham+FV), group Ⅲ (MI) and group Ⅳ (MI+FV). group Ⅱ and Ⅳ were treated with FV (10 mg·kg^-1·d^-1) for 4 weeks. The left ventricular structure, echocardiography and hydroxyproline were observed. The expression of caspase-3 was measured by immunohistochemistry and RT-PCR. RESULTS: Compared with MI group, there was a improvement of ultrastructure and index of left ventricular remodeling, and decrease in hydroxyproline in MI+FV group (all P<0.05). The number of caspase-3 positive cells also decreased in MI+FV group, and RT-PCR showed the level of caspase-3 mRNA expression was lower than that in MI group (P<0.05). CONCLUSION: Fluvastatin improves left ventricular remodeling after myocardial infarction, decreases the expression of caspase-3 and inhibits apoptosis.     

Cellular mechanisms of losartan on reversing left ventricular hypertrophy in spontaneously hypertensive rats

AIM:To investigate the role of proliferation and apoptosis in hypertensive left ventricular hypertrophy (LVH) and the effect of AT₁ blockade with losartan. METHODS:Left ventricles (LV) from 12, 24-week-old SHR (SHR₁₂, SHR₂₄), 24-week-old SHR treated with losartan (15 mg·kg^-1·d^-1, SHR-L₂₄) during 12 weeks, and age-matched WKY rats (WKY₁₂, WKY₂₄) were studied. Expression of PCNA was examined by immunohistochemistry. Apoptotic cells in LV sections were assessed by TUNEL method. Levels of fas mRNA were quantitated by RT-PCR. RESULTS: Compared with age-matched WKY, SHR₁₂ and SHR₂₄ showed increased LV hypertrophied index (HI), increased apoptotic index (AI) of myocytes (P＜0.01), but decreased AI of fibroblasts (P＜0.05). Moreover, SHR₁₂ exhibited increased PCNA labeling of myocytes (P＜0.05) with similar positive rates of fibroblasts.It was also showed that losartan reversed HI, significantly reduced the AI of myocytes and significantly increased the AI of fibroblasts. RT-PCR disclosed that levels of fas mRNA positively correlated with the frequency of apoptosis in LV of either SHR or WKY (r=0.52, P＜0.05). CONCLUSION:The cellular changes of LVH in adult SHR manifest as the imbalance between proliferation and apoptosis of myocytes, and insufficient apoptosis of fibroblasts. The mechanisms of losartan on reversing LVH may be mediated through adjusting the abnormal amount of cells and the expression of fas gene.     

Changes and clinical implications of plasma ANP,BNP and CNP levels in type 2 diabetic patients with vascular complications

AIM:To examine the changes and clinical implications of the plasma atrial natriuretic peptide (ANP), brain natriuretic peptide(BNP) and C-type natriuretic peptide(CNP) levels in type 2 diabetic patients with vascular complications. METHODS:9 subjects without diabetes, 34 diabetic patients without vascular complications and 23 diabetic patients with vascular complications were enrolled in the study and categorized into three groups. Plasma proANP, BNP fragment and N-terminal pro-CNP (NT-proCNP) were measured by enzyme linked immunosorbent assay (ELISA). The changes and associations of the plasma natriuretic peptide levels among three groups were analyzed. RESULTS:Compared with those in the controls and diabetics without vascular complications, the plasma proANP and BNP fragment levels in diabetic patients with vascular complications increased significantly (P<0.01). However, the plasma NT-proCNP level in this group decreased significantly (P<0.01). Nevertheless, no significant differences in the plasma proANP, BNP fragment and NT-proCNP levels among three subgroups (diabetics patients with macrovascular and/or microvascular complications) were observed (P>0.05). The plasma ANP level of diabetic patients with vascular complications was corelated significantly with the BNP levels (r=0.309, P<0.05). Furthermore, the ANP and BNP levels were correlated significantly with the CNP level (r=-0.374, P<0.05; r=-0.653, P<0.01). CONCLUSION:Measurement of the plasma ANP, BNP and CNP levels together may be a simple, cost-effective and reliable way to screen for diabetic patients with vascular complications.     

Changes of cytokine and collagen in the myocardial remodeling after acute myocardial infarction in rats

AIM:To clarify the relationship between the cytokine and collagen in myocardial remodeling after acute myocardial infarction (MI) in rats. METHODS:In MI group, Wistar rats were undergone acute myocardial infarction by ligation of the anterior descending coronary artery. Sham operation was made in rats as control. The mRNA expression of collagen and cytokines such as TNF-α and TGF-β1 in infract and non-infarct region of left myocardium were detected by RT-PCR at different time point (3 d, 1 and 4 weeks). RESULTS:Collagen type Ⅰ and Ⅲ elevated as well as the TNF-α and TGF-β1 in the MI group at 3th day. Expression of collagen type Ⅰ and Ⅲ were higher in the infarct region than that in the non-infarct region even at 4 weeks. TNF-α and TGF-β1 peaked at 1 week and declined gradually to the baseline, which was still higher than those in control group (P<0.01). Correlation analysis revealed that expressions of TNF-α and TGF-β1 were positively correlated with the collagen type Ⅰand Ⅲ (P<0.01). CONCLUSION:Cytokines participate in the myocardial remodeling after MI. Interfering with expression of cytokines may be the potentially preventative method in the myocardial remodeling.     

Effect of puerarin on monocrotaline-induced pulmonary hypertension and expression of chemokine CX3CL1/fractalkine

AIM: To observe the change of CX₃CL1/fractalkine (FKN) in the rats with monocrotaline-induced pulmonary hypertension, and to study the intervention of puerarin. METHODS: The pulmonary hypertension model was established in vivo by intraperitoneal injection of monocrotaline. Thirty male Sprague-Dawley rats (270-310 g) were randomly divided into 3 groups: control group (C), monocrotaline model group (M)and puerarin treatment group (M+P). The mean pulmonary arterial pressure (mPAP), mean right ventricular pressure (mRVP), mean carotid arterial pressure (mCAP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) were also detected. The structural changes of pulmonary arterioles were observed under optical microscope. Remodeling of lung blood vessels was determined by measuring the ratio of vessel wall area to total area (WA/TA) and the medium thickness of pulmonary artery (PAMT). The concentration of soluble fractalkine(sFKN) in plasma was measured by ELISA. The expression of FKN in the pulmonary artery wall was measured by immunohistochemistry. The mRNA level of FKN in the lung tissues was detected by RT-PCR.RESULTS: mPAP, mRVP, RV/(LV+S), WA/TA and PAMT in M group were higher than those in C group (P<0.01). RV/(LV+S), WA/TA and PAMT in M+P group were significantly lower than those in M group (P<0.01). No significant difference of mCAP among the 3 groups was observed. The levels of sFKN, FKN mRNA and FKN protein in M group were higher than those in C group (P<0.01), and the above data in M+P group were lower than those in M group(P<0.05). The serum level of sFKN had a positive correlation with PAMT and RV/(LV+S) (r＝0.719, r=0.685,respectively, P<0.01).CONCLUSION: Puerarin down-regulates the expression of FKN and suppresses the development of pulmonary hypertension and pulmonary vessel remodeling.     

Long-term insulin treatment improves postischemic cardiac structure and function via increasing serum BNP levels

AIM：To investigate the influence of long-term insulin treatment on postischemic cardiac structural and functional changes, and to further explore the underlying mechanisms. METHODS：Adult male SD rats were randomly divided into 4 groups (8~10 rats per group): sham group, myocardial infarction (MI) + saline (1 mL·kg-1·d-1, hypodermic injection for 4 weeks) group, MI + insulin (2 U·kg-1·d-1, hypodermic injection for 4 weeks) group and MI + insulin (2 U·kg-1·d-1, hypodermic injection for 4 weeks) + wortmannin ［a phosphatidylinositol 3-kinase (PI3K) inhibitor; 15 μg·kg-1·d-1, intraperitoneal injection 15 min before each insulin treatment］ group. The rats in the latter 3 groups were subject to ligation of the left anterior descending coronary artery, while those in sham group underwent the same surgical procedures without tying the sutures. The cardiac structural and functional changes were observed by echocardiogram, heart catheterization and microscopy with HE and Masson trichrome staining. Blood glucose was determined by Roche blood glucose meter, and the serum levels of insulin and brain natriuretic peptide (BNP) were detected by ELISA. The protein expression and phosphorylation of PI3K, Akt, glycogen synthase kinase 3β (GSK3β) and p38 mitogen-activated protein kinase (p38 MAPK) in myocardial tissues were detected by Western blotting. The mRNA expression of BNP, β-myosin heavy chain (β-MHC) and atrial natriuretic peptide (ANP) in myocardial tissues was determined by real-time fluorescence quantitative PCR. RESULTS：At the end of the 4th week, MI rats receiving long-term insulin treatment showed decreased ratio of heart length/heart weight, smaller systolic left ventricle cavity, thicker systolic interventricular septum, and increased cardiac ejection fraction, left ventricular development pressure and instantaneous first derivate of left ventricle pressure (P<0.05 vs MI + saline group). Moreover, insulin treatment significantly increased the phosphorylation of PI3K and Akt and the serum level of BNP, and inhibited the phosphorylation of p38 MAPK (P<0.05 vs MI + saline group), but did not change the mRNA expression of BNP in myocardial tissues. The effects of insulin on BNP were not blocked by wortmannin (P>0.05 vs MI + insulin group). CONCLUSION：Insulin improves postischemic cardiac structure and function by increasing serum BNP levels possibly independent of PI3K-Akt signaling pathway.     

Long-term effects of TCV116 on left ventricular remodeling and heart function after myocardial infarction in rats

AIM: To investigate the effects of long-term TCV116 on left ventricular remodeling and heart function after myocardial infarction. METHODS: Myocardial infarction (MI) was caused by ligation of the left anterior descending coronary artery in rats. One week after the surgical performance, the surviving rats were randomly assigned to the following treatment protocols: (1) MI rats with no therapy; (2) MI rats treated with TCV116 2 mg/kg per day; (3) Sham-operated control; (4) Sham-operated rats, treated with TCV116 2 mg/kg per day. At 22 weeks, cardiac hemodynamic parameters such as MAP, LVSP, dp/dt_max and LVEDP, and histomorphometric parameters such as LVW/BW and LVCA/BW were measured, mRNA of cardiac genes such as βMHC, BNP, TGF-β₁, collagen I and III were quantified, and survival rates were calculated. RESULTS: Compared with sham-operated rats, MI rats without therapy showed significant increases in histomorphometric parameters as well as in mRAN expressions of cardiac genes (P<0.01); While their hemodynamic parameters were significantly impaired (P<0.01), and survival duration shortened (P<0.05). Compared with MI rats without therapy, MI rats treated with TCV116 showed significant attenuation of mRAN expression of cardiac genes (P<0.01); While their hemodynamic parameters were significantly improved (P<0.05 or P＜0.01), and survival duration extended (P<0.05). CONCLUSION: Treatment with long-term angiotensin II type 1 receptor antagonist may improve left ventricular remodeling and cardiac function after MI in rats.     

Effects of fluvastatin on the left ventricular function,MHC gene expression and collagen remodeling after myocardial infarction

AIM: To observe the effects of fluvastatin (FV) on the left ventricular (LV) function, MHC mRNA and collagen remodeling of non-infarcted area after acute myocardial infarction (AMI). METHODS: Six hours after ligating left coronary artery, survivors of AMI female SD rats were randomly assigned to: ①AMI control; ②FV; ③sham-operated groups. After 8 weeks of therapy, the LV function, hemodynamics, expression of non-infarcted myocardial MHC mRNA, collagen volume fraction (CVF) and the ratio of type Ⅰ/Ⅲ collagen of non-infarcted area were assessed. RESULTS: Compared with sham-operated group, E wave, E wave deceleration, E/A ratio, LV end diastolic pressure (LVEDP), β MHC mRNA, CVF and the ratio of type Ⅰ/Ⅲ collagen were all significantly increased in AMI group, while fractional shortening (FS), ejection fraction (EF), mean arterial pressure (MAP) and α MHC mRNA were all significantly decreased. In comparison with AMI group, E wave, E wave deceleration, E/A, LVEDP, β MHC mRNA, CVF and the ratio of type Ⅰ/Ⅲ collagen were all significantly decreased, while FS, EF, MAP and α MHC mRNA were all significantly increased in FV group. CONCLUSION: FV improves the LV function after AMI and has beneficial effects on reversing LV myocardial pathologic switching of MHC isoform and collagen remodeling.     

Inflammation and coagulation activation are associated with gallstone formation in golden hamsters

AIM: To elucidate the relationship of inflammation, coagulation and cholesterol gallstone formation. METHODS: Hamsters were divided into four groups: control group (feeding normal diet), lithogenic diet (LD) 2 weeks group, LD 6 weeks group and LD+aspirin 6 weeks group. Gallstone incidence, antithrombin antigen (AT-Ⅲ:Ag), antithrombin activity (AT-Ⅲ:Ac), thrombin (F-Ⅱa:Ac), plasminogen activator inhibitor activity (PAI:Ac), plasmin activity (Plm:Ac), D-dimer:Ag and C-reactive protein (CRP) in gallbladder bile were observed as read-out parameters. RESULTS: The incidence of gallstones in control group, LD 2 weeks group, LD 6 weeks group and LD+aspirin group were 0%, 20%, 73% and 25%, respectively. AT-Ⅲ:Ag, F-Ⅱa:Ac, D-dimer and CRP in LD 2 weeks group and LD 6 weeks group were significantly higher than those in the control group (P<0.01). AT-Ⅲ:Ag, PAI:Ac, Plm:Ac, D-dimer and CRP in LD 6 weeks group were significantly higher than those in LD 2 weeks group (P<0.01). AT-Ⅲ:Ag, F-Ⅱa:Ac, PAI:Ac, D-dimer and CRP were strikingly decreased in LD+aspirin group compared with those in LD 6 weeks group (P<0.01). The level of CRP was closely correlated with the concentration of D-dimer (γ=0.752, P<0.01). CONCLUSIONS: Coagulation cascade is activated and crosslinked fibrin forms in gallbladder bile before gallstone formation. “Lithogenic bile” might play a central role in the inflammation of gallbladder mucosa, which activates extrinsic coagulation pathway and leads cholesterol gallstone formation.     

Effects of carvedilol,cilazapril and their combination on left ventricular remodeling after acute myocardial infarction in rats

AIM:To compare the effects of carvedilol, cilazapril and their combination on left ventricular remodeling(LVRM) after acute myocardial infarction(AMI) in rats. METHODS: Twenty-four hours after AMI operation, 100 surviving rats were randomly assigned to: ①AMI control(n= 25), ②AMI+carvedilol(1 mg·kg^-1 ·d^-1, n= 25)(C1), ③AMI+cilazapril(1 mg·kg^-1 ·d^-1, n= 25)(Z1), and ④ AMI+combination(n= 25) groups. Sham-operated group(n= 17) were selected randomly. After 4 weeks of therapy with the drugs gastric gavage, hemodynamic and pathological studies were performed. RESULTS: There were no significant differences in MI size among the four AMI groups(all P> 0.05) Left ventricular(LV) end diastolic pressure(LVEDP), volume(LVV), weight(LVW) and septal thickness(STh) were all higher and left ventricular pressure maximal rate of rise and fall(±d p /d t) were lower(all P< 0.01) in AMI group than sham-operated group. The LVEDP, LVV, LVW and STh were all lower and ±dp /dt were higher in Z1, C1, and combination groups than those in AMI group(P< 0.05, P< 0.01), with LVEDP and STh were more lower in the combination group than in the two monotherapy group(P< 0.05, P< 0.01), but there were no significant differences in other variables among the three therapy groups. CONCLUSION: Carvedilol, cilazapril and their combination all can prevent from LVRM after AMI in rats, improve hemodynamics and LV function, with the combination superior.     

Synergistic effect of hypertension and type 2 diabetes on cardiac dysfunction and myocardial remodeling in mice

AIM: To investigate whether the effect of hypertension combined with diabetic can lead to cardiac dysfunction and myocardial remodeling in mice. METHODS: The diabetic mice and non-diabetic mice of 14 weeks old were administered with PBS or angiotensin II (Ang II) for 4 weeks to induce mild hypertension. The left ventricular (LV) function was assessed by echocardiography and dobutamine stress test. The LV tissues were subjected to HE staining to assess cardiac hypertrophy. The phospharylated adenosine monophosphate-activated protein kinase (p-AMPK) levels in the LV tissues were determined by Western blotting. RESULTS: Compared with control group, diabetic mice (DM group) neither displayed marked cardiac dysfunction nor myocardial remodeling. Ang II treatment did not affect body weight and glucose level, but the blood pressure was increased in the diabetic and control mice. Ang II-induced LV hypertrophy in diabetic mice was significantly higher than that in control mice as assessed by LV masses and cardiomyocyte sizes. Moreover, Ang II-treatment reduced LV fractional shortening and contractility in the diabetic mice, but not in the control mice. The p-AMPK levels were significantly reduced in Ang II group, DM group and DM+Ang II group. CONCLUSION: The cardiac function and cardiac structure of type 2 diabetic mice did not obviously change. Cardiac dysfunction and myocardial remodeling were easily induced in type 2 diabetic mice when hypertension happened, suggesting that hypertension is a critical factor of cardiac dysfunction and myocardial remodeling in type 2 diabetic mice.     

Effects of irbesartan and perindopril on pressure overload-induced cardiac hypertrophy in rats

AIM: To observe the effects of irbesartan and perindopril on pressure-overload cardiac hypertrophy in rats. METHODS: 40 male adult Sprague Dawley rats were divided into 5 groups. One was sham operation group, other four were aortic banding groups. One week after operation, all rats were gavaged with normal saline, perindopril, irbesartan or combination of perindopril and irbesartan. Morphometric determination, calcineurin (CaN) expression, CaN and sarcoplasmic reticulum (SR) Ca²⁺-ATPase activity were performed at the end of 6 weeks of drug intervention. RESULTS: Left ventricular mass index (LVMI), transverse diameter of myocardical cell (TDM), CaN activity were remarkably decreased after drug intervention and this decrease was most remarkable in the combination group. SR Ca²⁺-ATPase activity increased after drug intervention, especially in the combination group. CaN expression in myocardium were remarkably decreased after drug intervention. LVMI was positively correlated with TDM and CaN, negatively correlated with SR Ca²⁺-ATPase. CONCLUSION: Both irbesartan and perindopril decrease CaN activity, increase SR Ca²⁺-ATPase activity and combination of them has synergic effects on regressing of ventricular hypertrophy.     

Proportion of CD14+CD16+ monocytes in peripheral blood from patients with type 2 diabetic mellitus and effect of LPS and IL-15 on expression of STAT5 in monocytes

AIM: To characterize the proportion of CD14⁺CD16⁺ monocytes in peripheral blood from type 2 diabetes (T2DM) patients and to observe the response of CD14⁺CD16⁺ monocytes to lipopolysaccharide (LPS) and interleukin-15 (IL-15) for further exploring the potential mechanism of inflammatory immune response in the pathogenesis of T2DM. METHODS: Twenty-eight patients with T2DM and 20 healthy volunteers were enrolled in the study. The peripheral blood was collected for determining the percentage of CD14⁺CD16⁺ monocytes by flow cytometry. The peripheral blood mononuclear cells (PBMC) were isolated and subject to stimulation with LPS and IL-15 for 4 h. The protein expression of STAT5 was detected by Western blotting and the phosphorylated (p)-STAT5 was determined by Western blotting and immunofluorescence. Serum levels of 25-hydroxyvitamin D₃ and IL-6, and the concentrations of IL-6 and monocyte chemoattractant protein-1(MCP-1) in the culture supernatants were assessed by ELISA. Serum level of C-reactive protein (CRP) was measured by immunoturbidimetry. RESULTS: There were positive correlations between the quantity of CD14⁺CD16⁺ monocytes and serum levels of CRP and IL-6 (r=0.394, P<0.05 and r=0.741, P<0.01), while serum 25 (OH) D₃ was negatively correlated with the quantity of CD14⁺CD16⁺ monocytes (r=-0.409, P<0.01), serum CRP(r=-0.479,P<0.01) and serum IL-6 (r=-0.774,P <0.01). After stimulated with LPS and IL-15, PBMC showed significant up-regulation of p-STAT5 protein expression, and significant increases in the supernatant levels of IL-6 and MCP-1 were observed (P<0.05). The expression of p-STAT5 existed in the nucleus.CONCLUSION: These findings suggest that the functional disturbance in monocytes occurs in T2DM, which may be related to insufficiency of vitamin D₃. The aberrant activation of STAT5 signaling pathway underlies the functional abnormalities of the monocytes in T2DM.     

Correlation between myocardial interstitial collagen remodeling and changes in hemodynamics in rats with myocardial infarction

AIM: To study the relationship between cardiac extracellular matrix remodeling and cardiac function after myocardial infarction. METHODS: We observed sequential changes in collagen contents and collagen Ⅰ/Ⅲ ratios in infarct zone (IZ) and non-infarct zone (NIZ) and their relationship to the parameters of left ventricular systolic and diastolic function in the rat model of myocardial infarction induced by ligation of left main coronary artery. RESULTS: Collagen conteants in IZ and NIZ after 3d of myocardial infarction were significantly higher than those in sham group at corresponding time (P<0.05, P<0.01). Collagen Ⅰ/Ⅲ ratio in IZ decreased on day 3, significantly increased after 7 d (P<0.01). Collagen Ⅰ/Ⅲ ratio in NIZ increased significantly afte14 d. Correlated analysis between collagen contents in IZ or NIZ and collagen type Ⅰ/Ⅲ ratio and maximal ascending velocity (+p'_max) or maximal descending velocity of the left ventricular pressure (-p'_max) was performed and the negative correlation between collagen contents in NIZ and +P'_max (r=-0.589, P>0.05) and -P'_max (r=-0.788, P<0.01) was found. Collagen content in IZ positively correlated to the +P'_max (r=0.70, P<0.50), but not to -P'_max (r=-0.29, P>0.05). Collagen type Ⅰ/Ⅲ ratios in NIZ correlated negatively to the +P'_max (r=-0.504, P>0.05) and -P'_max (r=-0.545, P>0.05), but there were no relationship between collagen type Ⅰ/Ⅲ ratios in IZ and +P'_max or -P'_max in IZ. CONCLUSION: Collagen deposition in IZ after myocardial infarction was of benefit to improvement of systolic function. Collagen deposition in NIZ was harmful to systolic and diastolic function.     

Inhibitory effects of right cervical sympathetic trunk transection on inflammatory response after acute myocardial infarction in rats and its influence on HMGB1/TLR4/NF-κB signaling pathway

AIM: To observe the effects of transection of right cervical sympathetic trunk (TCST) on inflammatory response and expression of high mobility group box 1 (HMGB1) and TLR4/NF-κB signaling pathway in the rats after acute myocardial infarction (AMI). METHODS: AMI model was established by ligation of left anterior descending coronary artery in SD rats, then the model rats were randomly divided into MI group and MI+TCST group. MI+TCST model was performed by transection of right cervical sympathetic trunk after left anterior descending coronary artery ligation. The rats in MI group and MI+TCST group were divided into 1, 3, 7, 14 and 28 d subgroups, and another sham operation group threading without ligation, with 8 rats in above each group. After modeling for 4 weeks, the cardiac function was measured by echocardiography. All rats were killed to harvest the hearts for mesuring cardiac hypertrophy index. The myocardial tissue close to infarction was observed with HE staining. The relative mRNA expression levels of HMGB1, tumor necrosis factor α(TNF-α) and interleukin (IL)-6 at different time points were detected by real-time PCR. The protein expression of HMGB1 and TLR4 at different time points after AMI was determined by Western blot. The effect of transection of right cervical sympathetic trunk on the expressions of HMGB1 and TLR4/NF-κB signaling pathway was also analyzed.RESULTS: Compared with the MI group, left ventricular ejection fraction (LVEF) and left ventricular shorterning fraction (LVFS) were significantly higher (P<0.05), left ventricular end-diastole dimension (LVEDd), left ventricular end-systole dimension (LVESd) and cardiac hypertrophy index were significantly lower (P<0.05), and the mRNA levels of HMGB1, TNF-α and IL-6 decreased significantly in MI+TCST group (P<0.05). Western blot results revealed that the protein expression level of HMGB1 increased in the infarct border zone at 3 d, and reached its peak at 7 d, then gradually decreased, and at 28 d after MI in MI group was still significantly higher than that in sham group (P<0.05). The protein expression of TLR4 was consistent with that of HMGB1. Transection of right cervical sympathetic trunk reduced protein expression of HMGB1 and TLR4/NF-κB signaling pathway-related proteins (P<0.05).CONCLUSION: Transection of right cervical sympathetic trunk improves ventricular remodeling and maintaining cardiac function. The mechanism may be related to inhibiting HMGB1/TLR4/NF-κB signaling pathway to reduce inflammatory response.     

Relationship between airway inflammation and pulmonary arterial remodeling in rats with chronic bronchitis and emphysema

AIM:To study the effects of airway and pulmonary inflammation on pulmonary arterial remodeling in rats with chronic bronchitis (CB) and emphysema.METHODS:Twenty-four male Wistar rats were divided into three groups (n=8): Group A: four-weeks CB and emphysema;Group B: six-weeks CB and emphysema group;Group C: normal control.The rat model of CB and emphysema was established by intratracheal instillation of lipopolysaccharide (LPS) and daily exposure to cigarette smog.The arterial blood gas analysis,pulmonary hemodynamics changes and cell counts in bronchoalveolar lavage fluid (BALF) were measured.The pathomorphological changes of airway inflammation,alveoli destruction and pulmonary arterial remodeling were observed by HE straining and triple straining.RESULTS:(1) The characteristic pathological changes of CB and emphysema were observed in group A and B.Neutrophils were the main cells infiltrated into the walls of airway in group A.Lymphocytes and macrophages were the main cells in group B.(2) Right ventricular systolic pressure (RVSP),mean pulmonary arterial pressure (mPAP),the ratio of the weight of right ventricle/left ventricle and septum (RV/LV+S) in group A and B were significantly higher than those in group C (P<0.05).The amount of muscular artery (MA) in group A and B were significantly higher than that in group C (P<0.05).(3) In group A and B,the levels of MA,RVSP,mPAP and RV/LV+S was correlated positively with the average alveolar area,the total cell counts and differential cell counts of neutrophils,lymphocytes and macrophages in BALF,and the level of infiltration into the walls of airway,respectively (P<0.05).The positive correlation was observed with the percentage of neutrophils,lymphocytes and macrophages between group A and B (P<0.05).The amounts of MA were also correlated positively with RVSP,mPAP and RV/LV+S (P<0.05).CONCLUSIONS:(1) The pulmonary artery hypertension,the right ventricular hypertrophy and the pulmonary arterial remodeling appeared before hypoxia.These may be related with the degree of the pulmonary inflammation.(2) The characteristic of pulmonary arterial remodeling was small artery organization,and correlated positively with the changes of hemodynamics.     

Level of copeptin for early prediction of cardiorenal syndrome in rats

AIM: To study the value of copeptin (CPP) level for the prediction of cardiorenal syndrome (CRS) in the rats with subtotal nephrectomy (SNX) combined with myocardial infarction (MI).METHODS: Male SD rats (n=60) were divided into blank control group (Con group), renal failure group (SNX group), heart failure group (MI group) and heart failure+renal failure group (CRS group). The concentrations of CPP in the serum and urine, hemodynamic indexes, blood pressure and renal function indexes were measured 1~5 weeks after modeling. The predictive value of CPP for CRS in the rats was evaluated by the receiver operating characteristic (ROC) curve.RESULTS: Compared with Con group, left ventricular systolic pressure (LVSP) at 9 d in CRS group was significantly decreased (P<0.05), left ventricular end-diastolic pressure (LVEDP) at 9 d in CRS group was significantly increased (P<0.05), and the difference of blood pressure at each time point was not statistically significant. The levels of blood urea nitrogen (BUN) and urinary creatinine (UCr) in CRS group were significantly increased at 1 and 3 weeks (P<0.05). Compared with Con group, serum CPP level was significantly increased at 1, 3 and 5 weeks (P<0.05), and urine CPP level was significantly increased at 3 weeks in CRS group. Serum brain natriuretic peptide (BNP) level was significantly increased at 1 and 3 weeks, while urine BNP level was significantly increased at 5 weeks after modeling in CRS group (P<0.05). No correlation between serum or urine CPP and BNP or BUN levels at 1 week in CRS group was observed. The results of ROC curve analysis indicated that the area under the curve (AUC) of serum CPP was 0.908 (95% CI:0.789~1.028), and the cut-off value was 56.59 ng/L (sensitivity 0.875, specificity 0.800).CONCLUSION: The combination of SNX and MI establishes a CRS rat model with both heart and kidney injury, and serum CPP can be used as a sensitive and specific biomarker for early prediction of CRS.     

Association between plasma level of microRNA-21 and pulmonary hypertension in heart failure patients with preserved ejection fraction

AIM: To investigate the correlation between microRNA-21 (miR-21) and pulmonary hypertension(PH) in the patients with heart failure with preserved ejection fraction (HFpEF). METHODS: From January 2014 to February 2016, 102 HFpEF patients presenting to Jiangxi Provincial People's Hospital were enrolled in this study. The patients were divided into PH-HFPEF group (n=36, PASP ≥ 50 mmHg) and HFpEF group (n=40, PASP<50 mmHg). Another 36 age-and sex-matched subjects served as healthy controls. The plasma level of miR-21 and its correlations with clinic data were examined, and multivariate logistic regression analysis was performed to identify the independent predictors of PH-HFpEF. Receiver operating characteristic (ROC) curve was analyzed, and the area under the curve (AUC) was calculated. The sensitivity and specificity for PH-HFPEF diagnosis were also determined. RESULTS: Age, plasma endothelin-1 (ET-1), interleukin-6 (IL-6), brain natriuretic peptide (BNP) and left atrial diameter (LAD) were significantly higher in PH-HFPEF group than those in HFPEF group (P<0.05). The level of miR-21 was significantly increased in PH-HFPEF group compared with HFpEF group and healthy control group. In addition, the miR-21 level was correlated with PASP (r=0.267, P=0.000), plasma IL-6 (r=0.302, P=0.013) and left ventricular mass index (LVMI) (r=0.515, P=0.036). Plasma IL-6 was positively correlated with plasma ET-1 (r=0.622, P=0.002). PASP was positively correlated with plasma IL-6 (r=0.36, P=0.023), ET-1 (r=0.76, P=0.004), BNP (r=0.43,P=0.031), and LAD (r=0.39, P=0.044). ROC curve showed that the AUC of miR-21 was 0.80. Multivariate logistic regression analysis showed that miR-21, LAD and BNP were the independent predictors of PH-HFpEF. CONCLUSION: Increased plasma miR-21 level is positively correlated to PH-HFpEF, and is an independent predictor of PH-HFpEF, suggesting that plasma miR-21 might be a useful new biomarker for predicting PH in HFpEF patients.