Generation of a Human Induced Pluripotent Stem Cell Line Expressing a Magnetic Resonance Imaging Reporter Gene.

The objective of the current study is to develop a new method for tracking transplanted human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) using magnetic resonance imaging (MRI). The CRISPR/dCas9 activation system is employed to overexpress ferritin heavy chain (FHC) in hiPSC-CMs. The mRNA and protein expression of FHC in hiPSC and hiPSC-CMs significantly increased after transfection. Iron chloride does not affect the cell viability in a concentration range from 0 to 2000 µm. hiPSCs overexpressing FHC (hiPSC- FHCOE) and hiPSC-CMs overexpressing FHC (hiPSC-CM-FHCOE) significantly enhanced cellular uptake of iron chloride but with no changes in electrophysiological properties compared to hiPSC-CM-Control. Furthermore, hiPSC-CM-FHCOE presented robust contrast and lower T2* values, signifying their potential as highly effective candidates for cardiac MRI. Next, hiPSC-CM-FHCOE is injected into mouse hearts and after 3 days of transplantation, MR images are obtained. hiPSC-CM-FHCOE cells exhibited clear signals in the hearts with lower T2* and rapid signal decay. Collectively, data from this proof-of-concept study demonstrated that endogenous labeling with FHC in hiPSC-CMs can be a potent strategy for enhancing the accuracy of cardiac MRI. This technology represents a significant step forward in tracking the transplanted hiPSC-CMs in the hearts of live animals.

Local decorin delivery via hyaluronic acid microrods improves cardiac performance, ventricular remodeling after myocardial infarction.

Heart failure (HF) remains a global public health burden and often results following myocardial infarction (MI). Following injury, cardiac fibrosis forms in the myocardium which greatly hinders cellular function, survival, and recruitment, thus severely limits tissue regeneration. Here, we leverage biophysical microstructural cues made of hyaluronic acid (HA) loaded with the anti-fibrotic proteoglycan decorin to more robustly attenuate cardiac fibrosis after acute myocardial injury. Microrods showed decorin incorporation throughout the entirety of the hydrogel structures and exhibited first-order release kinetics in vitro. Intramyocardial injections of saline (n = 5), microrods (n = 7), decorin microrods (n = 10), and free decorin (n = 4) were performed in male rat models of ischemia-reperfusion MI to evaluate therapeutic effects on cardiac remodeling and function. Echocardiographic analysis demonstrated that rats treated with decorin microrods (5.21% ± 4.29%) exhibited significantly increased change in ejection fraction (EF) at 8 weeks post-MI compared to rats treated with saline (-4.18% ± 2.78%, p < 0.001) and free decorin (-3.42% ± 1.86%, p < 0.01). Trends in reduced end diastolic volume were also identified in decorin microrod-treated groups compared to those treated with saline, microrods, and free decorin, indicating favorable ventricular remodeling. Quantitative analysis of histology and immunofluorescence staining showed that treatment with decorin microrods reduced cardiac fibrosis (p < 0.05) and cardiomyocyte hypertrophy (p < 0.05) at 8 weeks post-MI compared to saline control. Together, this work aims to contribute important knowledge to guide rationally designed biomaterial development that may be used to successfully treat cardiovascular diseases.

Inhibition of galectin-3 post-infarction impedes progressive fibrosis by regulating inflammatory profibrotic cascades.

AIMS: Acute myocardial infarction (MI) causes inflammation, collagen deposition, and reparative fibrosis in response to myocyte death and, subsequently, a pathological myocardial remodelling process characterized by excessive interstitial fibrosis, driving heart failure (HF). Nonetheless, how or when to limit excessive fibrosis for therapeutic purposes remains uncertain. Galectin-3, a major mediator of organ fibrosis, promotes cardiac fibrosis and remodelling. We performed a preclinical assessment of a protein inhibitor of galectin-3 (its C-terminal domain, Gal-3C) to limit excessive fibrosis resulting from MI and prevent ventricular enlargement and HF. METHODS AND RESULTS: Gal-3C was produced by enzymatic cleavage of full-length galectin-3 or by direct expression of the truncated form in Escherichia coli. Gal-3C was intravenously administered for 7 days in acute MI models of young and aged rats, starting either pre-MI or 4 days post-MI. Echocardiography, haemodynamics, histology, and molecular and cellular analyses were performed to assess post-MI cardiac functionality and pathological fibrotic progression. Gal-3C profoundly benefitted left ventricular ejection fraction, end-systolic and end-diastolic volumes, haemodynamic parameters, infarct scar size, and interstitial fibrosis, with better therapeutic efficacy than losartan and spironolactone monotherapies over the 56-day study. Gal-3C therapy in post-MI aged rats substantially improved pump function and attenuated ventricular dilation, preventing progressive HF. Gal-3C in vitro treatment of M2-polarized macrophage-like cells reduced their M2-phenotypic expression of arginase-1 and interleukin-10. Gal-3C inhibited M2 polarization of cardiac macrophages during reparative response post-MI. Gal-3C impeded progressive fibrosis post-MI by down-regulating galectin-3-mediated profibrotic signalling cascades including a reduction in endogenous arginase-1 and inducible nitric oxide synthase (iNOS). CONCLUSION: Gal-3C treatment improved long-term cardiac function post-MI by reduction in the wound-healing response, and inhibition of inflammatory fibrogenic signalling to avert an augmentation of fibrosis in the periinfarct region. Thus, Gal-3C treatment prevented the infarcted heart from extensive fibrosis that accelerates the development of HF, providing a potential targeted therapy.

Local delivery of decorin via hyaluronic acid microrods improves cardiac performance and ventricular remodeling after myocardial infarction.

Heart failure (HF) is a global public health burden and associated with significant morbidity and mortality. HF can result as a complication following myocardial infarction (MI), with cardiac fibrosis forming in the myocardium as a response to injury. The dense, avascular scar tissue that develops in the myocardium after injury following MI creates an inhospitable microenvironment that hinders cellular function, survival, and recruitment, thus severely limiting tissue regeneration. We have previously demonstrated the ability of hyaluronic acid (HA) polymer microrods to modulate fibroblast phenotype using discrete biophysical cues and to improve cardiac outcomes after implantation in rodent models of ischemia-reperfusion MI injury. Here, we developed a dual-pronged biochemical and biophysical therapeutic strategy leveraging bioactive microrods to more robustly attenuate cardiac fibrosis after acute myocardial injury. Incorporation of the anti-fibrotic proteoglycan decorin within microrods led to sustained release of decorin over one month in vitro and after implantation, resulted in marked improvement in cardiac function and ventricular remodeling, along with decreased fibrosis and cardiomyocyte hypertrophy. Together, this body of work aims to contribute important knowledge to help develop rationally designed engineered biomaterials that may be used to successfully treat cardiovascular diseases.

Increased vulnerability to atrial and ventricular arrhythmias caused by different types of inhaled tobacco or marijuana products.

BACKGROUND: The emergence of a plethora of new tobacco products marketed as being less harmful than smoking, such as electronic cigarettes and heated tobacco products, and the increased popularity of recreational marijuana have raised concerns about the potential cardiovascular risk associated with their use. OBJECTIVE: The purpose of this study was to investigate whether the use of novel tobacco products or marijuana can cause the development of proarrhythmic substrate and eventually lead to arrhythmias. METHODS: Rats were exposed to smoke from tobacco, marijuana, or cannabinoid-depleted marijuana, to aerosol from electronic cigarettes or heated tobacco products, or to clean air once per day for 8 weeks, following by assays for blood pressure, cardiac function, ex vivo electrophysiology, and histochemistry. RESULTS: The rats exposed to tobacco or marijuana products exhibited progressively increased systolic blood pressure, decreased cardiac systolic function with chamber dilation, and reduced overall heart rate variability, relative to the clean air negative control group. Atrial fibrillation and ventricular tachycardia testing by ex vivo optical mapping revealed a significantly higher susceptibility to each, with a shortened effective refractory period and prolonged calcium transient duration. Histological analysis indicated that in all exposure conditions except for air, exposure to smoke or aerosol from tobacco or marijuana products caused severe fibrosis with decreased microvessel density and higher level of sympathetic nerve innervation. CONCLUSION: These pathophysiological results indicate that tobacco and marijuana products can induce arrhythmogenic substrates involved in cardiac electrical, structural, and neural remodeling, facilitating the development of arrhythmias.

Impairment of Endothelial Function by Cigarette Smoke Is Not Caused by a Specific Smoke Constituent, but by Vagal Input From the Airway.

BACKGROUND: Exposure to tobacco or marijuana smoke, or e-cigarette aerosols, causes vascular endothelial dysfunction in humans and rats. We aimed to determine what constituent, or class of constituents, of smoke is responsible for endothelial functional impairment. METHODS: We investigated several smoke constituents that we hypothesized to mediate this effect by exposing rats and measuring arterial flow-mediated dilation (FMD) pre- and post-exposure. We measured FMD before and after inhalation of sidestream smoke from research cigarettes containing normal and reduced nicotine level with and without menthol, as well as 2 of the main aldehyde gases found in both smoke and e-cigarette aerosol (acrolein and acetaldehyde), and inert carbon nanoparticles. RESULTS: FMD was reduced by all 4 kinds of research cigarettes, with extent of reduction ranging from 20% to 46% depending on the cigarette type. While nicotine was not required for the impairment, higher nicotine levels in smoke were associated with a greater percent reduction of FMD (41.1±4.5% reduction versus 19.2±9.5%; P=0.047). Lower menthol levels were also associated with a greater percent reduction of FMD (18.5±9.8% versus 40.5±4.8%; P=0.048). Inhalation of acrolein or acetaldehyde gases at smoke-relevant concentrations impaired FMD by roughly 50% (P=0.001). However, inhalation of inert carbon nanoparticles at smoke-relevant concentrations with no gas phase also impaired FMD by a comparable amount (P<0.001). Bilateral cervical vagotomy blocked the impairment of FMD by tobacco smoke. CONCLUSIONS: There is no single constituent or class of constituents responsible for acute impairment of endothelial function by smoke; rather, we propose that acute endothelial dysfunction by disparate inhaled products is caused by vagus nerve signaling initiated by airway irritation.

Deciphering mechanism of the herbal formula WuShen in the treatment of postinfarction heart failure.

BACKGROUND: Numerous clinical studies reported the effectiveness of herbal formula WuShen (WS) in treating cardiovascular diseases, yet relevant basic research was rarely conducted. METHODS AND RESULTS: Twelve main bioactive compounds of WS decoction were identified using the ultra-performance liquid chromatography-LTQ-Orbitrap mass spectrometer. A total of 137 active compounds with 613 targets were predicted by network pharmacology; their bioinformatic annotation and human microarray data suggested that wounding healing, inflammatory response, and gap junction were potentially the major therapeutic modules. A rat model of post-myocardial infarction (MI) heart failure (HF) was used to study the effects of WS on cardiac function, adverse cardiac remodeling, and experimental arrhythmias. Rats treated with WS led to a significantly improved pump function and reduced susceptibility to both ventricular tachycardia and atrial fibrillation, and restricted adverse cardiac remodeling partly via inhibiting TGFß1/SMADs mediated extracellular matrix deposition and Rac1/NOX2/CTGF/Connexin43 -involved gap junction remodeling. CONCLUSIONS: The present study highlights that WS can be applied to the treatment of heart failure and the upstream therapy for atrial fibrillation and ventricular tachycardia through its preventive effect on adverse cardiac remodeling.

Injectable Drug-Releasing Microporous Annealed Particle Scaffolds for Treating Myocardial Infarction.

Intramyocardial injection of hydrogels offers great potential for treating myocardial infarction (MI) in a minimally invasive manner. However, traditional bulk hydrogels generally lack microporous structures to support rapid tissue ingrowth and biochemical signals to prevent fibrotic remodeling toward heart failure. To address such challenges, a novel drug-releasing microporous annealed particle (drugMAP) system is developed by encapsulating hydrophobic drug-loaded nanoparticles into microgel building blocks via microfluidic manufacturing. By modulating nanoparticle hydrophilicity and pregel solution viscosity, drugMAP building blocks are generated with consistent and homogeneous encapsulation of nanoparticles. In addition, the complementary effects of forskolin (F) and Repsox (R) on the functional modulations of cardiomyocytes, fibroblasts, and endothelial cells in vitro are demonstrated. After that, both hydrophobic drugs (F and R) are loaded into drugMAP to generate FR/drugMAP for MI therapy in a rat model. The intramyocardial injection of MAP gel improves left ventricular functions, which are further enhanced by FR/drugMAP treatment with increased angiogenesis and reduced fibrosis and inflammatory response. This drugMAP platform represents a new generation of microgel particles for MI therapy and will have broad applications in regenerative medicine and disease therapy.

Salvianolic acid B protects against myocardial ischaemia-reperfusion injury in rats via inhibiting high mobility group box 1 protein expression through the PI3K/Akt signalling pathway.

Salvianolic acid B (Sal B) has a significant protective effect on myocardial ischaemia-reperfusion (I/R) injury. Therefore, the aims of this study were to determine the effects of Sal B on myocardial ischaemic-reperfusion (I/R) injury in rats and to explore whether its underlying mechanism of cardioprotection occurs through activating the expression of the phosphoinositide 3-kinase/protein, kinase B (PI3K/Akt) and inhibiting the expression of high mobility group protein 1 (HMGB1). Ninety Sprague-Dawley rats were randomized into five groups: group 1 (sham-operated), group 2 (myocardial I/R), group 3 (low dose of Sal B+I/R), group 4 (high dose of Sal B+I/R), and group 5 (high dose of Sal B+I/R+LY294002, which is a specific PI3k inhibitor). All I/R rats received 30 min myocardial ischaemia followed by 24-h reperfusion. Cardiac function, infarct size, myocardial injury marker levels, inflammatory response and cardiomyocyte apoptosis as well as Bcl-2, Bax, P-Akt, HMGB1 and TLR4 expression were measured. In the current study, Sal B significantly ameliorated myocardial I/R injury in a dose-dependent manner, ameliorated cardiac function, reduced myocardial infarction size, decreased myocardial injury marker expression, decreased inflammatory responses, reduced apoptosis, activated PI3K/Akt expression and inhibited HMGB1 expression. However, all effects of Sal B were significantly reversed by LY294002. Overall, the present study indicated that Sal B attenuated myocardial I/R injury by activating PI3K/Akt and inhibiting the release of HMGB1 in rats.

Chronic Kidney Disease Increases Atrial Fibrillation Inducibility: Involvement of Inflammation, Atrial Fibrosis, and Connexins.

Chronic kidney disease (CKD) causes atrial structural remodeling and subsequently increases the incidence of atrial fibrillation (AF). Atrial connexins and inflammatory responses may be involved in this remodeling process. In this study, nephrectomy was used to produce the CKD rat model. Three months post-nephrectomy, cardiac structure, function and AF vulnerability were quantified using echocardiography and electrophysiology methods. The left atrial tissue was tested for quantification of fibrosis and inflammation, and for the distribution and expression of connexin (Cx) 40 and Cx43. An echocardiography showed that CKD resulted in the left atrial enlargement and left ventricular hypertrophy, but had no functional changes. CKD caused a significant increase in the AF inducible rate (91.11% in CKD group vs. 6.67% in sham group, P < 0.001) and the AF duration [107 (0-770) s in CKD vs. 0 (0-70) s in sham, P < 0.001] with prolonged P-wave duration. CKD induced severe interstitial fibrosis, activated the transforming growth factor-ß1/Smad2/3 pathway with a massive extracellular matrix deposition of collagen type I and α-smooth muscle actin, and matured the NLR (nucleotide-binding domain leucine-rich repeat-containing receptor) pyrin domain-containing protein 3 (NLRP3) inflammasome with an inflammatory cascade response. CKD resulted in an increase in non-phosphorylated-Cx43, a decrease in Cx40 and phosphorylated-Cx43, and lateralized the distribution of Cx40 and Cx43 proteins with upregulations of Rac-1, connective tissue growth factor and N-cadherin. These findings implicate the transforming growth factor-ß1/Smad2/3, the NLRP3 inflammasome and the connexins as potential mediators of increased AF vulnerability in CKD.

Salvianolate reduces atrial fibrillation through suppressing atrial interstitial fibrosis by inhibiting TGF-ß1/Smad2/3 and TXNIP/NLRP3 inflammasome signaling pathways in post-MI rats.

BACKGROUND: Salvianolate is the main water-soluble bioactive compound of Salvia Miltiorrhiza Bunge and is now clinically used in the treatment of cardiovascular diseases in China. However, its applications in the prevention of atrial interstitial fibrosis (AIF) and atrial fibrillation (AF) are not fully revealed. PURPOSES: To investigate the preventive effect of salvianolate on the pathogenesis of AF in post-myocardial infarction (MI) rats and to elucidate the potential mechanisms. MATERIALS AND METHODS: Rats underwent left anterior descending coronary artery ligation were randomized into four groups and administered intraperitoneally with vehicle (MI group, n = 13), or 10, 20 and 40 mg/kg salvianolate (Sal-L, Sal-M and Sal-H group, n = 13, 14 and 13 respectively) for totally five weeks. Rats underwent sham operation was used as control group (Sham, n = 10). Then, echocardiography and AF inducibility test were detected. Tissues and serum were collected for Sirius red and fast green counter stain or hematoxylin-eosin to assess atrial interstitial fibrosis and hypertrophy, or for western blot and ELISA analysis. RESULTS: Salvianolate injection significantly improved cardiac function, reduced left atrial enlargement and P-wave duration, and decreased not only the vulnerability to AF but also AF duration. Histologic analysis showed that salvianolate mitigated AIF and atrial hypertrophy. Western blot analysis found that salvianolate inhibited the TGFß1/Smad2/3 mediated-collagen deposition and inhibited the TXNIP/NLRP3 inflammasome /IL-1ß and IL-18 signal pathway. ELISA analysis showed that salvianolate significantly reduced the serum concentrations of BNP, IL-6, CRP and TGFß1. CONCLUSIONS: Salvianolate may constitute a novel upstream therapy for AF by suppressing AIF. The underlying mechanism may be attributable to its inhibitory effects on TGF-ß1/Smad2/3 and TXNIP/NLRP3 inflammasome signaling pathway.

Shensong Yangxin capsule reduces atrial fibrillation susceptibility by inhibiting atrial fibrosis in rats with post-myocardial infarction heart failure.

PURPOSE: Shensong Yangxin (SSYX) capsule is a traditional Chinese medicine that has been used widely to treat cardiac arrhythmia. This study aimed to assess whether SSYX prevents atrial fibrillation (AF) after chronic myocardial infarction (MI)-induced heart failure and to determine the underlying mechanisms. MATERIALS AND METHODS: The study included 45 male Sprague Dawley rats. The rats underwent MI induction or sham surgery. One week after MI induction surgery, we performed serial echocardiography and administered SSYX capsule to some rats that experienced MI. After 4 weeks of treatment, AF inducibility was assessed with transesophageal programmed electrical stimulation technology. Additionally, multielectrode array assessment, histological analysis, and Western blot analysis were performed. RESULTS: AF inducibility was significantly lower in SSYX rats than in MI rats (33.3% vs 73.3%, P<0.05). Additionally, conduction velocities in the left atrium were greater in SSYX rats than in MI rats. Moreover, SSYX decreased left atrial fibrosis, downregulated TGF-ß1, MMP-9, TIMP-I, and type I and III collagen expressions, and inhibited the differentiation of cardiac fibroblasts to myofibroblasts. CONCLUSION: SSYX reduces AF inducibility after MI by improving left atrial conduction function via the inhibition of left atrial fibrosis. It prevents the development of an MI-induced vulnerable substrate for AF.

DL-3-n-butylphthalide improves ventricular function, and prevents ventricular remodeling and arrhythmias in post-MI rats.

DL-3-n-butylphthalide (NBP) is used in the treatment of ischemic stroke. It was demonstrated NBP also has a cardioprotective effect in acute myocardial infarction (MI) model. However, the chronic effects of NBP on ventricular function, remodeling, and arrhythmias in post-MI stage are unknown. This study was to investigate the effect of NBP on reducing ventricular remodeling and arrhythmias in post-MI stage. Post-MI rats were randomly treated with 100 mg/kg NBP daily (n = 21) or vehicle (n = 21) for 5 weeks. Sham-operated rats were treated with the same dose vehicle (n = 18). Echocardiographic assessment, ventricular arrhythmias inducibility test, morphological and collagen analysis, immunohistochemistry, and western blot were studied. NBP significantly improved cardiac function, inhibited the severity and inducibility of ventricular arrhythmias, reduced cardiac index, fibrosis and hypertrophy, improved the protein expression and distribution of Cx43 gap junction, and upregulated PI3k/Akt/Nrf2 pathway and the downstream antioxidant response elements (ARE), including heme oxygenase-1, Glutathione, Cu-Zn superoxide dismutase, and Fe/Mn superoxide dismutase. These results suggest NBP improves LV function and reduces ventricular arrhythmias by mitigating LV fibrosis, hypertrophy, and Cx43 gap junction remodeling. PI3k/Akt/Nrf2/ARE signaling pathway may contribute to its anti-ventricular remodeling effects.

3,7-Bis(2-hydroxyethyl)icaritin, a potent inhibitor of phosphodiesterase-5, prevents monocrotaline-induced pulmonary arterial hypertension via NO/cGMP activation in rats.

Pulmonary arterial hypertension (PAH) is a chronic progressive disease which leads to elevated pulmonary arterial pressure and right heart failure. 3,7-Bis(2-hydroxyethyl)icaritin (ICT), an icariin derivatives, was reported to have potent inhibitory activity on phosphodiesterase type 5 (PDE5) which plays a crucial role in the pathogenesis of PAH. The present study was designed to investigate the effects of ICT on monocrotaline (MCT)-induced PAH rat model and reveal the underlying mechanism. MCT-induced PAH rat models were established with intragastric administration of ICT (10, 20, 40 mg/kg/d), Icariin (ICA) (40 mg/kg/d) and Sildenafil (25 mg/kg/d). The mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. Pulmonary artery remodeling was assessed by H&E staining. Blood and lung tissue were collected to evaluate the level of endothelin 1 (ET-1), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The expressions endothelial nitric oxide synthase (eNOS) and PDE5A in lung tissues were determined by Western blot analysis. The results showed that ICT reduced RVHI and mPAP, and reversed lung vascular remodeling in rats with MCT-induced PAH. ICT also reversed MCT-induced ET-1 elevation, NO and cGMP reduction in serum or lung tissue. Moreover, ICT administration significantly induced eNOS activation and PDE5A inhibition. ICT with lower dose had better effects than ICA. In summary, ICT is more effective in preventing MCT-induced PAH in rats via NO/cGMP activation compared with ICA. These findings demonstrate a novel mechanism of the action of ICT that may have value in prevention of PAH.

DL-3-n-Butylphthalide reduces atrial fibrillation susceptibility by inhibiting atrial structural remodeling in rats with heart failure.

Agents against atrial structural remodeling (ASR) are thought to block the occurrence of atrial fibrillation (AF). The aim of this study was to investigate the effects of DL-3-n-butylphthalide (NBP) on ASR and AF formation in rats with heart failure (HF) induced by myocardial infarction. The heart failure rats established 1 week after ligating left anterior descending coronary artery were randomly treated with vehicle (HF group, n = 24), or treated with DL-3-n-butylphthalide (100 mg/kg body weight) (NBP group, n = 26) for 4 weeks. Eighteen rats that underwent the same surgery but without ligating artery treated with vehicle were used as sham group (n = 18). Echocardiography, AF inducibility test, atrial fibrosis, gap junction, cytokine expression and serum antioxidant capacity analysis were detected at follow-up. Treatment of NBP for 4 weeks significantly improved cardiac function (P < 0.05), reduced AF inducibility and duration time (P < 0.05), and attenuated atrial fibrosis (P < 0.05). NBP also up-regulated protein expression of both overall Cx43 and phosphorylated Cx43 (P < 0.05) and improved the distribution of Cx43. Furthermore, NBP significantly inhibited the expression of TNF-α, NF-κB, and TGF-ß1 and up-regulated Nrf2 and HO-1 protein expression with an increased serum T-AOC, CAT, and SOD activities and a reduced serum MDA. Collectively, NBP prevented ASR and AF in rats with HF by inhibiting atrial fibrosis, resynchronizing gap junction remodeling through inhibiting TNF-α/NF-κB/TGF-ß1-related inflammatory reactions, and up-regulating Nrf2/HO-1-mediated antioxidant effects. Therefore, NBP may be a promising agent as upstream therapy for the prevention of AF.

Traditional Chinese Medicine ShenZhuGuanXin Granules Mitigate Cardiac Dysfunction and Promote Myocardium Angiogenesis in Myocardial Infarction Rats by Upregulating PECAM-1/CD31 and VEGF Expression.

BACKGROUND: Myocardial infarction (MI) is the main cause of global mortality and morbidity despite the development of therapeutic approaches. ShenZhuGuanXin granules (SG) have been shown to possess cardioprotective effects against coronary heart disease (CHD). However, little is known about its specific mechanism. The present study aimed to investigate the therapeutic effect of SG in cardiac dysfunction and to demonstrate whether SG can promote myocardium angiogenesis by establishing a rat model of myocardial infarction with left anterior descending ligating. METHODS AND RESULTS: Three days after MI, rats were randomly divided into six groups: sham group (sham), MI group (MI), MI + low dose SG (SG-L) group, MI + middle dose SG (SG-M) group, MI + high dose SG (SG-H) group, and MI + compound Danshen dropping pills (CDDP) group as a positive control. Four weeks after administration, rats underwent hemodynamics and echocardiography study. Ventricle tissues were processed for histology and immunohistochemistry studies. Compared with MI group, SG treatment dose-dependently improved cardiac hemodynamic function, attenuated infarct size, increased microvessel density, and increased the expression of PECAM-1/CD31 and VEGF. CONCLUSIONS: SG dose-dependently improved cardiac hemodynamic function and attenuated infarct size by promoting angiogenesis through upregulating PECAM-1/CD31 and VEGF expression.