An Aspirin-Free Versus Dual Antiplatelet Strategy for Coronary Stenting: STOPDAPT-3 Randomized Trial.

BACKGROUND: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials. METHODS: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin. RESULTS: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group. CONCLUSIONS: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.

[Surgical Treatment for Giant Coronary Aneurysm Complicated by Acute Myocardial Infarction and Cardiopulmonary Arrest:Report of a Case].

Giant coronary aneurysm is rare, but a life-threatening disease. We report a 67-year-old man with 39 mm coronary aneurysm. He was presented to our facility with acute coronary syndrome complicated by cardiogenic shock. Angiography demonstrated giant coronary aneurysm and occlusion of the right coronary artery. After cardiopulmonary resuscitation and cardiopulmonary support (PCPS), emergent excision of aneurysm and coronary artery bypass grafting was performed. The postoperative course was good without complications. Most giant coronary artery aneurysms are asymptomatic but some patients present with angina pectoris, sudden death, fistula formation, pericardial tamponade, compression of surrounding structures, or congestive heart failure. But once complications, such as thrombosis, distal embolization, fistula formation or rupture occurred, it is difficult to save life without aggressive surgery. At present, there are no specific guidelines for the treatment of giant coronary aneurysm. Surgical correction is a preferred approach for the treatment of giant coronary artery aneurysms.

Prediction of age and brachial-ankle pulse-wave velocity using ultra-wide-field pseudo-color images by deep learning.

This study examined whether age and brachial-ankle pulse-wave velocity (baPWV) can be predicted with ultra-wide-field pseudo-color (UWPC) images using deep learning (DL). We examined 170 UWPC images of both eyes of 85 participants (40 men and 45 women, mean age: 57.5 ± 20.9 years). Three types of images were included (total, central, and peripheral) and analyzed by k-fold cross-validation (k = 5) using Visual Geometry Group-16. After bias was eliminated using the generalized linear mixed model, the standard regression coefficients (SRCs) between actual age and baPWV and predicted age and baPWV from the UWPC images by the neural network were calculated, and the prediction accuracies of the DL model for age and baPWV were examined. The SRC between actual age and predicted age by the neural network was 0.833 for all images, 0.818 for central images, and 0.649 for peripheral images (all P < 0.001) and between the actual baPWV and the predicted baPWV was 0.390 for total images, 0.419 for central images, and 0.312 for peripheral images (all P < 0.001). These results show the potential prediction capability of DL for age and vascular aging and could be useful for disease prevention and early treatment.

The Role of Saline and Sodium Bicarbonate Preprocedural Hydration to Prevent Mid-term Renal Insufficiency in Patients with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention.

Objective Persistent renal damage (RD) three months after exposure to contrast media is associated with contrast-induced acute kidney injury (CI-AKI) and poor clinical outcomes. Little is known about the role of preprocedural hydration on persistent RD in patients with chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2] undergoing percutaneous coronary intervention (PCI). We therefore examined the use of preprocedural hydration to decrease the incidence of persistent RD. Methods Between 2012 and 2015, 1,230 consecutive patients undergoing PCI, except for patients with an eGFR ≥60 mL/min/1.73 m2, on dialysis, having acute myocardial infarction, or recently having started renin-angiotensin inhibitors, were screened (n=333). Before their index PCI, the 12-h saline group (n=103) received 1 mL/kg/h 0.9% sodium chloride for 12 hours, and the 1-h bicarbonate group (n=63) received 3 mL/kg 154 mEq/L sodium bicarbonate for 1 hour. The control group (n=167) received no pre-procedural hydration. The study outcome of kidney function decline was investigated using the percent-change (%-change) of the calculated creatinine clearance between the baseline value and the lowest value recorded three to six months after index PCI. Results There was less renal function deterioration in the saline group than in the control group, and the bicarbonate group showed deterioration similar to the other groups (%-change; 12-h saline 2.0±11.3% vs. control -5.6±12.6%, p<0.001; vs. 1-h bicarbonate -1.8±14.1%, p=0.18; 1-h bicarbonate vs. control, p=0.14 ANOVA). A multiple regression analysis adjusted for risk factors for persistent RD showed that saline hydration correlated independently with a higher %-change (r=0.262, p<0.001). Conclusion Preprocedural 12-h saline may be better than no preprocedural hydration in preventing mid-term renal insufficiency in CKD patients undergoing PCI.

Effects of azilsartan compared to other angiotensin receptor blockers on left ventricular hypertrophy and the sympathetic nervous system in hemodialysis patients.

Hypertension is a major risk factor for cardiovascular and cerebrovascular events, and most patients with hypertension are administered antihypertensive drugs. However, not all patients achieve normal blood pressure levels. The new angiotensin receptor blocker azilsartan (Takeda Pharmaceutical Company Limited, Osaka, Japan) has been reported to have a strong hypotensive effect. Our study investigated the efficacy of azilsartan compared with other angiotensin receptor blockers. This study included 17 hypertensive patients on HD, who had been administered angiotensin receptor blockers, except for azilsartan, for more than 6 months before enrolling, and after enrollment, they were switched to azilsartan. Blood tests, Holter electrocardiogram, ambulatory blood pressure monitoring, and echocardiography were performed at baseline and at the 6-month follow-up. The blood pressure from baseline to 6 months had significantly decreased (24-h systolic blood pressure from 150.9 ± 16.2 mm Hg to 131.3 ± 21.7 mm Hg, P = 0.008), awakening time systolic blood pressure from 152.1 ± 16.9 mm Hg to 131.7 ± 23.2 mm Hg, P = 0.01, sleep-time systolic blood pressure from 148.1 ± 19.7 mm Hg to 130.0 ± 20.1 mm Hg, P = 0.005). There was a significant reduction in serum noradrenaline levels as well as left ventricular mass index after switching to azilsartan (from 550.1 ± 282.9 pg/mL, to 351.7 ± 152.3 pg/mL, P = 0.002; from 117.0 ± 26.4 g/m(2) to 111.3 ± 23.9 g/m(2), P = 0.01, respectively). Azilsartan had a significantly stronger hypotensive effect than other angiotensin receptor blockers. Thus, the switch to azilsartan might improve prognosis of hemodialysis patients. We suggest that the strong anti-hypertensive effect of azilsartan originated from a combination of primary angiotensin receptor blocker class-effect and a stronger suppression of sympathetic nervous system.

Intravascular ultrasound complements the diagnostic capability of carbon dioxide digital subtraction angiography for patients with allergies to iodinated contrast medium.

Carbon dioxide digital subtraction angiography (CO(2)DSA) is a useful and safe alternative for patients with renal dysfunction or allergies to iodinated contrast medium. However, CO(2)DSA image quality is worse than that of angiography with iodinated contrast medium, primarily because of movement during imaging and stent struts. In angioplasty of arteries of the lower extremities, CO(2)DSA cannot be used to sufficiently evaluate target lesions and determine the most efficient intervention. However, in the current case report, we describe a patient with severe allergies to iodinated contrast medium (Stevens-Johnson syndrome), because of which we were unable to use any iodinated contrast medium when conducting angioplasty. Therefore, we used intravascular ultrasound (IVUS), which facilitated the complete observation of the target lesion after stent implantation without requiring iodinated contrast medium. In this case, IVUS was used to complement the diagnostic capabilities of CO(2)DSA.

Patient with a massive idiopathic thrombosis in the inferior vena cava.

A 50 year-old man with no significant medical history was admitted for dyspnea and left femoral swelling. Contrast-enhanced computed tomography revealed pulmonary thromboembolism (PTE) and a thrombus in the inferior vena cava (IVC). The thrombus extended from the proximal IVC to the left popliteal vein. Therefore, we decided that an IVC filter insertion was difficult to indicate. Urgent IVC and peripheral vein thrombectomy was performed under cardiopulmonary bypass. On postoperative day 1, venous ultrasonography showed residual deep vein thrombosis in the left external iliac-femoral vein and the popliteal vein. The IVC filter insertion was performed to prevent the recurrence of PTE.

[Combined double valve replacement and abdominal aortic aneurysm repair in a patient with infective endocarditis; report of a case].

The choice of simultaneous or staged surgery in patients with valvular diseases and abdominal aortic aneurysms (AAA) remains controversial. We present a case of simultaneous surgery of double valve replacement and abdominal aorta replacement in a patient with infective endocarditis. A 74-year-old woman was admitted to our hospital because of general fatigue and appetite loss. Computed tomography (CT) scan showed a infrarenal AAA measuring 99 x 67 mm. Echocardiography showed severe regurgitation of mitral valve and aortic valve with vegetations. Electrocardiogram showed atrial fibrillation. She was diagnosed as heart failure due to infective endocarditis and treated with antibiotics, diuretics and catecholamine. However, heart failure did not improve; the patient underwent double valve replacement, pulmonary vein isolation and abdominal aorta replacement simultaneously. Postoperative course was uneventful.

Cough syncope induced by gastroesophageal reflux disease.

A 52-year-old Japanese man was admitted to our hospital for evaluation of syncope and convulsions. An electrocardiogram on admission revealed normal sinus rhythm. However, after repeated bouts of coughing, the heart rate showed bradycardia associated with convulsion. He was diagnosed with cough syncope secondary to laryngopharyngitis, which was caused by gastroesophageal reflux disease (GERD). Once the patient was administrated lansoprazole (Takeda Pharmaceutical Co., Osaka, Japan) for GERD, the syncope disappeared. The causes of syncope are diverse and may manifest in disorders of different organ systems in the body. Therefore, clinicians should perform a careful whole body examination to obtain the correct diagnosis.

The long-acting Ca2+-channel blocker azelnidipine prevents left ventricular remodeling after myocardial infarction.

Long-acting Ca(2+)-channel blockers have been reported to be effective in treating ischemic heart disease. However, their effects on cardiac remodeling after myocardial infarction (MI) are still unclear. We performed this study to examine the effect of azelnidipine on left ventricular (LV) remodeling, including systolic and diastolic dysfunction, in rats with MI. MI was induced by ligation of the left anterior descending artery. The rats were then separated into 3 groups: a sham-operated group (n = 9), untreated MI group (n = 10), and azelnidipine-treated MI group (n = 10). Four weeks after MI, hemodynamic measurements and Doppler echocardiographic assessment were performed. LV weight and LV end-diastolic dimension were significantly higher in the untreated MI group than in the sham-operated group. Azelnidipine significantly prevented the increases in these parameters. Azelnidipine also improved the ejection fraction (42 +/- 3%, P<0.05) and the E wave to A wave ratio (3.2 +/- 0.5, P<0.05), compared with the untreated MI group (31 +/- 3% and 5.3 +/- 0.8, respectively). In conclusion, azelnidipine can prevent LV remodeling and improve systolic and diastolic function after MI. Administration of long-acting Ca(2+)-channel blockers after MI is an effective strategy for treating MI.

Effects of treatment for diabetes mellitus on circulating vascular progenitor cells.

The circulating endothelial progenitor cells (EPCs) have an important role in angiogenesis, and the smooth muscle progenitor cells (SMPCs) participate in atherosclerosis. However, little is known about the effects of treatment of diabetes mellitus (DM) on EPCs and SMPCs. Therefore, we investigated the relations between the number of circulating vasucular progenitor cells before and after the treatment for DM. Ten previously untreated DM patients were enrolled in this study. Blood samples were collected before and after treatment. The peripheral mononuclear cells were purified and cultured to differentiate them into EPCs and SMPCs. After two weeks, the number of EPCs was determined by Dil-labeled acetylated low density lipoprotein and lectin binding. The number of SMPCs was evaluated by immunocytochemical staining of alpha-smooth muscle actin. Before treatment, the number of EPCs and SMPCs was significantly related to hemoglobin A1c and blood sugar. Serial examination revealed that improvement of glycemic control significantly increased the number of both EPCs and SMPCs. DM reduces the number of circulating EPCs and SMPCs according to its severity, and treatment of DM significantly increases the number of EPCs and SMPCs, which may be involved in angiogenesis and atherosclerosis in diabetes.

The effects of HMG-CoA reductase inhibitor on vascular progenitor cells.

Circulating bone marrow-derived vascular progenitor cells contribute to angiogenesis, atherosclerosis, and the response to vascular injury. These vascular progenitor cells consist of two cell groups, endothelial progenitor cells (EPCs) and smooth muscle progenitor cells (SMPCs). Although HMG-CoA reductase inhibitors (statins) have been reported to inhibit atherosclerosis partially by increased EPCs, the effects of statins on SMPCs are unclear. Therefore, we investigated the relationship between EPCs and SMPCs and whether pravastatin has atheroprotective effects on SMPCs. Peripheral mononuclear cells (MNCs) were isolated and cultured on fibronectin-coated dishes in SMPC medium. MNCs were stained with acetylated low density lipoprotein and lectin, or alpha-smooth muscle actin, and cell numbers were counted. mRNA expression and vascular endothelial growth factor (VEGF) protein synthesis of MNCs were evaluated. Pravastatin significantly increased the number of EPC and decreased the number of SMPC. mRNA expression of VEGF, endothelial nitric oxide synthase, VEGF receptor-2 (KDR), and Akt were up-regulated, and VEGF secretion was increased by pravastatin. The present study demonstrated that pravastatin has promotive effects on the differentiation from MNCs to EPC cells, while inhibitory effects to SMPC cells. Our findings suggest a previously unreported mechanism of the effect of statin therapy on vascular progenitor cells.

Effects of erythropoietin on cardiac remodeling after myocardial infarction.

Erythropoietin (EPO) has been suggested to have a cardioprotective effect against ischemia. The purpose of this study was to examine the effects of EPO on cardiac remodeling after myocardial infarction (MI). MI was induced by ligation of the coronary artery in Wistar rats. The rats with MI were randomly divided into untreated MI and two EPO-treated MI groups. EPO was administered subcutaneously by injection once a day for 4 days after MI at 5000 U/kg or 3 times a week for 4 weeks at 1000 U/kg. Five days after MI, EPO prevented the increase in activated caspase 3, matrix metalloproteinase-2, and transcriptional activation of activator protein-1 in non-infarcted myocardium. Four weeks after MI, left ventricular weight, left ventricular end-diastolic pressure, and left ventricular dimension were increased, and ejection fraction and E wave deceleration time were decreased. EPO significantly attenuated this ventricular remodeling and systolic and diastolic dysfunction. In addition, EPO significantly attenuated the interstitial fibrosis and remodeling-related gene expression in non-infarcted myocardium. Furthermore, EPO significantly enhanced angiogenesis and reduced apoptotic cell death in peri-infarcted myocardium. In conclusion, when administered after MI, EPO prevents cardiac remodeling and improves ventricular function with enhanced angiogenesis and reduced apoptosis.

Comparison of levels of serum matrix metalloproteinase-9 in patients with acute myocardial infarction versus unstable angina pectoris versus stable angina pectoris.

Matrix metalloproteinases (MMPs) are important for resorption of extracellular matrixes and may degrade the fibrous cap of an atherosclerotic plaque, thus contributing to coronary plaque rupture. Histologic studies have shown MMP expression in lesions of acute coronary syndrome. In this study, we evaluated the relation between plaque morphology as obtained by intravascular ultrasound before percutaneous coronary intervention and serum MMP levels in patients who had coronary artery disease. We enrolled consecutive 47 patients who had acute myocardial infarction (AMI), 23 who had unstable angina pectoris (UAP), and 19 who had stable effort angina pectoris and underwent intravascular ultrasound before percutaneous coronary intervention followed by successful primary percutaneous coronary intervention. Peripheral blood was obtained from all patients before angiography and serum levels of MMP-1,-2, and -9 were analyzed. Serum levels of MMP-9 in the AMI and UAP groups were significantly higher than that in the stable effort angina pectoris group (p = 0.007 and 0.04, respectively). From the intravascular ultrasound findings before percutaneous coronary intervention, plaque rupture was detected in 26 patients (55%) in the AMI group and in 11 patients (48%) in the UAP group. In these 2 groups, patients with plaque rupture had significantly higher levels of MMP-9 than patients who did not have plaque rupture (p = 0.03 and 0.01, respectively). Multiple logistic regression analysis showed that MMP-9 was the only independent predictor of plaque rupture (p = 0.004). In conclusion, high levels of MMP-9 in patients who have AMI and UAP are related to the presence of plaque rupture in the culprit lesion.

Involvement of c-Jun NH2 terminal kinase and p38MAPK in rapamycin-mediated inhibition of neointimal formation in rat carotid arteries.

OBJECTIVE: Rapamycin-coated stents in coronary artery lesions have recently been shown to be effective in inhibiting neointimal formation. However, little is known about the effects of rapamycin on mitogen-activated protein kinase (MAPK), which is an important signal for neointimal formation. Therefore, we examined the effects of rapamycin on MAPK and transcriptional factors in cultured human coronary artery smooth muscle cells (CASMC) and in balloon-injured rat carotid arteries. METHODS AND RESULTS: Activation of ERK, JNK, p38MAPK, AP-1, and NF-kB in coronary artery smooth muscle cells was increased by 2% fetal bovine serum. Ten nmol/L of rapamycin prevented the activation of JNK, p38MAPK, AP-1, and NF-kB (65%, 65%, 67%, and 26% respectively, P<0.01). In an in vivo study, remarkable neointimal formation was observed 14 days after injury. Coating Pluronic gel with 20 and 50 mug rapamycin around the injured artery significantly decreased the intimal area/medial area ratio, compared with vehicle (0.75 vs. 1.2, P<0.01). Rapamycin prevented the increase in activation of JNK, p38MAPK, AP-1, and NF-kB in injured artery (42%, 70%, 75%, and 60% respectively, P<0.05). CONCLUSIONS: Neointimal formation after balloon injury is inhibited by rapamycin, which is partially mediated by inhibition of JNK and p38MAPK, followed by AP-1 and NF-kB.

Granulocyte-colony stimulating factor augments neovascularization induced by bone marrow transplantation in rat hindlimb ischemia.

Because granulocyte-colony stimulating factor (G-CSF) mobilizes bone marrow cells including endothelial progenitor cells, we examined whether G-CSF augments angiogenesis and collateral vessel formation induced by bone marrow-mononuclear cells transplantation (BMT). Unilateral hindlimb ischemia was surgically induced in Lewis rats. One week after surgery, administration of 100 mg/kg per day G-CSF significantly increased the laser Doppler blood perfusion index (LDBPI), number of angiographically detectable collateral vessels (angiographic score), and capillary density determined by alkaline phosphatase staining. In the BMT group (1 x 10(7) cells/rat) and the group with combined G-CSF treatment and BMT, LDBPI was significantly increased compared with that in the vehicle-treated group. In the BMT group, neovascularization was significantly increased as evidenced by the angiographic score and capillary density compared with the vehicle-treated group. Furthermore, the combination of G-CSF treatment and BMT augmented neovascularization compared with BMT alone, as evidenced by the angiographic score and capillary density. Moreover, G-CSF significantly increased vascular endothelial growth factor mRNA and fibroblast growth factor-2 mRNA in hindlimb muscle. In conclusion, G-CSF was found to augment neovascularization in rat hindlimb ischemia. Combined use of G-CSF treatment and BMT may be a useful strategy for therapeutic neovascularization in ischemic tissues.

Angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium after myocardial infarction.

Osteopontin has been reported to have an important role in cardiac fibrosis. However, little is known about the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin type 1 receptor blockers (ARB) on osteopontin expression in infarcted myocardium. The purpose of this study was to elucidate the effects of an ACEI (perindpril) and an ARB (candesartan cilexitil) on cardiac function as assessed by Doppler echocardiography and cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted rats. ACEI or ARB was administered after myocardial infarction (MI). At 4 weeks after MI, cardiac function, and mRNAs in non-infarcted myocardium were analyzed. ACEI and ARB equally prevented left ventricular dilatation, reduction of ejection fraction, and the increase in E/A wave velocity ratio and the rate of E wave deceleration by MI. ACEI and ARB significantly suppressed increased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, osteopontin, and collagen I and III in the non-infarcted ventricle at 4 weeks. Immunohistochemically stained osteopontin was increased in interstitial fibrosis of non-infarcted myocardium. Both ACEI and ARB significantly prevented cardiac fibrosis and osteopontin expression. In conclusion, angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium and prevents cardiac remodeling after MI.

Role of c-Jun NH2-terminal kinase in G-protein-coupled receptor agonist-induced cardiac plasminogen activator inhibitor-1 expression.

Plasminogen activator inhibitor-1 (PAI-1) has been implicated as a contributing risk factor for cardiovascular disease. However, little is known about molecular mechanisms of cardiac PAI-1 gene expression. To elucidate these mechanisms, dominant negative mutants of c-Jun NH(2)-terminal kinase (JNK), p38MAPK, apoptosis signal-regulating kinase-1 (ASK-1) and c-Jun were overexpressed in rat neonatal ventricular cardiac myocytes and fibroblasts by adenovirus vector to abrogate the activation of the corresponding endogenous proteins. One hundred nmol/l of angiotensin II significantly enhanced the JNK and p38MAPK activities of cardiomyocytes (2.3-fold and 1.9-fold, P < 0.05) and fibroblasts (3.2-fold and 2.5-fold, P < 0.05). At 3 h after stimulation, angiotensin II was found to have significantly increased PAI-1 mRNA, by 5.2-fold in cardiomyocytes and by 9.7-fold in fibroblasts. Dominant negative mutants of JNK, ASK-1 and c-Jun significantly inhibited PAI-1 mRNA expression and protein synthesis in both cardiomyocytes and fibroblasts, whereas a dominant negative mutant of p38MAPK did not change this expression. Moreover, a dominant negative mutant of JNK also significantly prevented the induction of PAI-1 mRNA expression by 100 nmol/l endothelin-1 and 10 micromol/l phenylephrine. In conclusion, G-protein-coupled receptor agonist-induced PAI-1 expression is partially mediated through JNK activation.

Effects of granulocyte-colony stimulating factor on cardiac remodeling after myocardial infarction.

BACKGROUND: Recent studies suggest that granulocyte colony-stimulating factor (G-CSF) may be beneficial in the treatment of myocardial infarction (MI). However, the effects of G-CSF on MI are still controversial and the molecular mechanism of G-CSF treatment for repair of the infarcted heart is not fully understood. METHODS: Mice were divided into three groups: Control, MI and MI treated with G-CSF. Four weeks after MI, we examined cardiac function by Doppler echocardiography and measured non-infarcted myocardial mRNA expression by northern blot analysis. RESULTS: Cardiac function decreased significantly in the MI groups compared with the sham-operated groups. Additionally, the ratios of E wave to A wave peak velocity (E/A) in the MI groups were higher than in the control group. E/A in G-CSF MI mice was significantly lower than in control MI mice (p<0.01). Matrix metalloproteinase-2 (MMP-2) mRNA expression was significantly increased in the MI groups compared with the control group (p<0.01). Furthermore, mRNA expression in the G-CSF MI group was significantly higher than in the Control MI group (p<0.05). CONCLUSIONS: G-CSF can prevent the LV remodeling process after MI that accompanies progressive cardiac dysfunction. One of the mechanisms of G-CSF treatment for cardiac remodeling after MI may be overexpression of MMP-2 in non-infarcted myocardium.