Icariin improves cardiac function and remodeling via the TGF-ß1/Smad signaling pathway in rats following myocardial infarction.

BACKGROUND: Postinfarction cardiac remodeling presents a compensatory mechanism aimed at mitigating congestive heart failure. It is distinguished by progressive dilatation and hypertrophy of the ventricular chambers, fibrotic alterations, and prolonged apoptosis of cardiomyocytes. The primary objective of this study was to assess the effects of icariin on myocardial fibrosis and ventricular remodeling in rats subjected to myocardial infarction (MI). METHODS: Male Sprague‒Dawley (SD) rats were subjected to randomization and subsequently divided into distinct groups: the control group, the sham group (undergoing sham operation), the MI group (experiencing ligation of the left anterior descending artery), and the icariin group. Within the icariin group, rats were further categorized into three different dose groups based on the administered icariin dosage: the MI30 group (30 mg/kg/day), the MI60 group (60 mg/kg/day), and the MI120 group (120 mg/kg/day). Cardiac function evaluation was carried out using echocardiography. Histological examinations, including hematoxylin and eosin (HE) staining, Masson staining, and immunohistochemistry studies, were conducted 90 days after the occurrence of MI. Additionally, Western blotting was employed to assess TGF-ß1, p-Smad2, and p-Smad3 levels. RESULTS: The administration of icariin revealed a noteworthy enhancement in cardiac function among rats afflicted with left anterior descending coronary artery (LAD) ligation. In comparison to the icariin groups, the MI group exhibited reduced EF and FS, along with elevated LVEDD and LVESD. Furthermore, the cardiac fibrosis levels in the MI group rats exhibited a considerable increase compared to those in the icariin group. Notably, the levels of Collagen I, Collagen III, MMP2, and MMP9 were significantly higher in the MI group than in the icariin group, with evident distinctions. Moreover, the expression levels of TGF-ß, IL-13, p-Smad2, and p-Smad3 were notably upregulated in the MI group compared to the icariin group. CONCLUSIONS: In an experimental rat model of MI, the administration of icariin resulted in the amelioration of both cardiac function and remodeling processes, operating through the intricate TGF-ß1/Smad signaling pathway.

The comparison of methods to identify the presence of fibrocytes in formalin-fixed, paraffin-embedded archival cardiac tissue with coronary heart disease.

The purpose of this study was to find the optimal technical approach to identify the presence of fibrocytes in formalin-fixed, paraffin-embedded archival cardiac tissue with CHD (coronary heart disease). Using the coexpression markers CD45 and αSMA, the presence of fibrocytes was examined by three different methods, including double immunohistochemistry staining, combination labeling of immunohistochemistry and immunofluorescence and double immunofluorescence labeling. Double immunohistochemistry staining was very difficult to identify the CD45(+)/αSMA(+) fibrocytes. Although combination staining of immunohistochemistry and immunofluorescence has made it possible to evaluate the co-localization of CD45 and αSMA in the fibrocytes, this method was prone to produce many false positive cells. In contrast, CD45(+)/αSMA(+) fibrocytes could be clearly recognized by double immunofluorescence labeling. In conclusion, double immunofluorescence labeling is the optimal technical approach to identify the presence of fibrocytes in routinely processed cardiac tissue with CHD.

Extracorporeal cardiac shock wave therapy ameliorates myocardial fibrosis by decreasing the amount of fibrocytes after acute myocardial infarction in pigs.

OBJECTIVES: Extracorporeal shock wave (SW) therapy ameliorates cardiac remodeling after acute myocardial infarction (AMI). However, it remains to be examined whether and how SW therapy ameliorates myocardial fibrosis after AMI. Fibrocytes are associated with myocardial fibrosis. Thus, we examined whether SW therapy ameliorates myocardial fibrosis and whether fibrocytes are associated after AMI in pigs. MATERIALS AND METHODS: AMI was created by coronary embolism. Twenty-five pigs were divided into three groups: AMI+SW group (AMI with SW therapy, n=15), AMI group (without SW therapy, n=5), and sham+SW group (SW therapy without AMI, n=5). The collagen area fraction was examined by Masson's trichrome staining. The presence of fibrocytes was identified by immunofluorescence and confocal microscopy. The location of CXCL12 was examined by immunohistochemistry. RESULTS: Compared with the AMI group, the AMI+SW group showed significantly ameliorated myocardial fibrosis in terms of collagen area fraction (27.21±8.13 vs. 10.13±4.96, P<0.05) and reduced fibrocytes (CD34/α-smooth muscle actin: 35.40±11.72 vs. 12.27±7.71, P<0.05; CXCR4/α-smooth muscle actin: 40.80±8.96 vs. 16.54±6.38, P<0.05). There were positive correlations between the collagen area fraction and the number of fibrocytes (r=0.936; P<0.05) and between the number of CXCR4 fibrocytes and the SDF-1/CXCL12 cells (r=0.802; P<0.05) in the three groups. CONCLUSION: The results show that SW therapy ameliorates myocardial fibrosis after AMI in pigs, which is associated with the decreased amount of fibrocytes.

Fibrocytes are associated with the fibrosis of coronary heart disease.

Fibrocytes contribute significantly to fibrosis in many cardiac diseases. However, it is not clear whether fibrocytes are associated with the fibrosis in coronary heart disease (CHD). The aim of this study was to determine whether fibrocytes are involved in cardiac fibrosis in CHD. We identified the presence of fibrocytes in CHD heart by immunofluorescence and confocal microscopy, examined the collagen volume fraction by Masson's Trichrome staining, and evaluated the correlation between fibrocytes and cardiac fibrosis. In conjunction, we examined the location of CXCL12, a homing factor and specific ligand for CXCR4, by immunohistochemistry. Fibrocytes were identified in 26 out of 27 CHD hearts and in 10 out of 11 normal hearts. Combinations, including CD34/αSMA, CD34/procollagen-I, CD45/αSMA, CXCR4/procollagen-I and CXCR4/αSMA, stained significantly more fibrocytes in CHD hearts as compared with those in normal hearts (p<0.05). There were positive correlations between the collagen volume fraction and the amount of fibrocytes (r=0.558; p=0.003<0.01) and between the number of CXCR4(+) fibrocytes and the CXCL12(+) cells (r=0.741; p=0.000<0.01) in CHD hearts. Based upon these findings, we conclude that fibrocytes, likely recruited through the CXCR4/CXCL12 axis, may contribute to the increase in the fibroblast population in CHD heart.

A modified regimen of extracorporeal cardiac shock wave therapy for treatment of coronary artery disease.

BACKGROUND: Cardiac shock wave therapy (CSWT) improves cardiac function in patients with severe coronary artery disease (CAD). We aimed to evaluate the clinical outcomes of a new CSWT treatment regimen. METHODS: The 55 patients with severe CAD were randomly divided into 3 treatment groups. The control group (n = 14) received only medical therapy. In group A ( n = 20), CSWT was performed 3 times within 3 months. In group B ( n = 21), patients underwent 3 CSWT sessions/week, and 9 treatment sessions were completed within 1 month. Primary outcome measurement was 6-minute walk test (6MWT). Other measurements were also evaluated. RESULTS: The 6MWT, CCS grading of angina, dosage of nitroglycerin, NYHA classification, and SAQ scores were improved in group A and B compared to control group. CONCLUSIONS: A CSWT protocol with 1 month treatment duration showed similar therapeutic efficacy compared to a protocol of 3 months duration. CLINICAL TRIAL REGISTRY: We have registered on ClinicalTrials.gov, the protocol ID is CSWT IN CHINA.

[Extracorporeal cardiac shock wave therapy improved myocardial micro-vascular circulation after acute myocardial infarction at early stage in pigs].

OBJECTIVE: To explore the effect of low-energy extracorporeal shock wave therapy to improve myocardial micro-vascular circulation after acute myocardial infarction at the early stage in pig model. METHODS: A total of 25 domestic pigs were used in this study. Model of acute myocardial infarction (AMI) was created successfully by the implantation of angioplasty balloon in mid-distal segment of left anterior descending coronary artery (n=20). These AMI animals were divided two groups. Extracorporeal shock wave therapy to the ischemic myocardial region was performed for the group of shock wave therapy (n=15) at 3 days after acute myocardial infarction; The remaining AMI animals were treated in the same manner, but without the shock wave therapy (n=5), The other health animals (n=5) were used as blank control group. The number of endothelium cell, capillary density, VEGF mRNA level and collateral vessel Rentrop score in each group were evaluated and compared. RESULTS: Shock wave treatment up-regulated the mRNA expression of VEGF in the model of acute myocardial infarction (P < 0.05). Furthermore, the number of capillaries was significantly higher in the shock wave group than that of positive and blank control group (P < 0.05). The Rentrop score of collateral vessel indicated the reconstruction of collateral circulation in shock wave group. CONCLUSION: Extracorporeal cardiac shock wave therapy could effectively induce angiogenesis, up-regulate the expression of angiogenic factor, resulting in an improvement in micro-vascular circulation reconstruction of ischemic myocardial region.

[Extracorporeal cardiac shock wave therapy for treatment of coronary artery disease].

OBJECTIVE: To evaluate the feasibility and efficiency of extracorporeal cardiac shock wave therapy (CSWT) for treatment of coronary artery disease. METHODS: Twenty-five patients with 1 - 16 years history of chronic angina pectoris underwent the CSWT. Before and after the treatment, low-dose Dobutamine stress echocardiography and (99)Tc(m)-MIBI myocardial perfusion SPECT were applied to locate the ischemic segments, detect the viable myocardium and evaluate the effect of CSWT. Under the guidance of echocardiography, CSWT was applied in R-wave-triggered manner with low energy (0.09 mJ/mm(2)) at 200 shoots/spot for 9 spots (-1-0-+1 combination). Patients were divided group A and group B. Sixteen patients in group A were applied 9 sessions on 29 segments within 3 month and nine patients in group B were applied 9 sessions on 13 segments within 1 month. Ten chronic angina pectoris patients receiving standard medication served as controls. RESULTS: All patients completed the 9 sessions without procedural complications or adverse effects. CSWT significantly improved symptoms as evaluated by NYHA, Canadian Cardiovascular Society (CCS) class sores, Seattle angina questionnaire (SAQ), 6-min walk and the use of nitroglycerin (P < 0.05). CSWT also improved myocardial perfusion and regional myocardium function as evaluated by rest SPECT and stress peak systolic strain rate (PSSR) (P < 0.01). Myocardial perfusion improvement was more significant in group A compared with group B (1.21 ± 0.86 vs. 0.83 ± 0.80, P < 0.01). All parameters remained unchanged in control group during follow up. CONCLUSION: These preliminary results indicate that CSWT is safe and effective on ameliorating anginal symptoms for chronic angina pectoris patients.

Cardiac shock wave therapy reduces angina and improves myocardial function in patients with refractory coronary artery disease.

BACKGROUND: Safe and effective therapeutic management of refractory coronary artery disease (CAD) in heart patients is critical to enhance cardiovascular function and improve quality of life. Current therapies for refractory CAD are inadequate in ameliorating angina and promoting revascularization of ischemic myocardium. HYPOTHESIS: Cardiac shock wave therapy (CSWT) is a safe and effective noninvasive intervention in the management of patients with refractory CAD. METHODS: The study enrolled 9 male patients age 50 to 70 years (5.11 ± 5.46 years) with a diagnosis of CAD and stent implantation (3.00 ± 2.24 stents). CSWT was carried out for 3 months at 3 intervals during the first week of each month (first, third, and fifth day), for a total of 9 therapies per patient. Dobutamine stress echocardiography and radionuclide angiography identified the myocardial ischemic segments. The effects of CSWT on myocardial perfusion and systolic function were examined. Other outcome measures included myocardial injury enzyme markers, angina scale, nitroglycerin dosage, and cardiopulmonary fitness assessments. RESULTS: Improved myocardial blood flow and regional systolic function (stress peak systolic strain rate - 1.10 to - 1.60 s(-1), P = 0.002) were detected in patients following CSWT. Reductions in creatine kinase (87.89 ± 36.69 to 86.22 ± 35.96 IU/L, P = 0.046), creatine kinase MB (10.89 ± 5.73 to 10.11 ± 5.93 IU/L, P = 0.008), aspartate transaminase (interquartile range [IQR], 28.00 to 27.00 IU/L, P = 0.034) were also found. Angina (Canadian Cardiovascular Society scale IQR 3.0 to 2.0, P = 0.035) and nitroglycerin dose reduction (IQR 3.0 to 1.0 times/wk, P = 0.038) were reported. CONCLUSIONS: This study is a preliminary assessment of CSWT in patients with refractory CAD. We report that CSWT is a noninvasive, effective, and safe intervention in the treatment of refractory CAD.