scholarly journals Are activated B cells involved in the process of myocardial fibrosis after acute myocardial infarction? An in vivo experiment

2020 ◽  
Author(s):  
Fanrui Mo ◽  
Ying Luo ◽  
Yuluan Yan ◽  
Juan Li ◽  
Shayi Lai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
B Cells ◽  
B Cell ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Tnf Α ◽  
Myocardial Collagen ◽  
Tgf Β1 ◽  
Activated B Cells

Abstract Background Inflammatory cells infiltrate into the ischemic and hypoxic myocardial tissue after myocardial infarction. B cells gather at the site of myocardial injury and secrete cytokines to regulate immune inflammation and fiber repair processes. Methods The animal experiment used ligation of the left anterior descending (LAD) artery of C57BL/6 mice to establish a mouse acute myocardial infarction (AMI) model to observe changes in activated B cells and cytokines at different time points. Twelve-week-old C57BL/6 male mice were randomly divided into the Sham group (24 mice) (thread under the LAD artery without ligation) and the AMI group (64 mice). In addition, C57BL/6 B-cell knockout (BKO) mice and C57BL/6 wild-type (WT) mice were used to establish AMI models to observe the expression levels of cardiomyocyte cytokines, such as TNF-α IL-1β, IL-6, TGF-β1, COL1-A1, COL3-AIII, TIMP, and MMP9. Moreover, pathological and collagen changes in the myocardium were analysed. One-way ANOVA and LSD method was used for comparisons of multiple and pairwise groups respectively. P<0.05 indicated significant differences. Results An AMI model of C57BL/6 mice was established successfully. The ratio of activated B cells and the expression of TNF-α, IL-1β, IL-6, TGF-β1, and B cell activating factor (BAFF) in the 5-day subgroup were the highest in the myocardium, spleen and peripheral blood with the most obvious myocardial inflammatory cell infiltration. The cytokines mRNA expression levels in the 5-day subgroup of the BKO group were decreased compared with those in the WT group (P<0.05). Among the 2-week subgroups of the Sham, WT and BKO groups, the the LVEDd and LVESd of the BKO group were lower than those of the WT group (P<0.05), and the left ventricular ejection fraction (LVEF) was higher than that of the WT group (P<0.05). Conclusion Activated B cells participate in the sustained state of myocardial inflammation and immune system activation after AMI, and may affect the metabolism of myocardial collagen after AMI by secreting cytokines. Moreover, B cells promote the expression of myocardial collagen Type I and Type III and damage the left ventricular ejection function.

scholarly journals Are activated B cells involved in the process of myocardial fibrosis after acute myocardial infarction? An in vivo experiment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fanrui Mo ◽  
Ying Luo ◽  
Yuluan Yan ◽  
Juan Li ◽  
Shayi Lai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
B Cells ◽  
B Cell ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Tnf Α ◽  
Myocardial Collagen ◽  
Tgf Β1 ◽  
Activated B Cells

Abstract Background Inflammatory cells infiltrate into the ischemic and hypoxic myocardial tissue after myocardial infarction. B cells gather at the site of myocardial injury and secrete cytokines to regulate immune inflammation and fiber repair processes. Methods The animal experiment used ligation of the left anterior descending (LAD) artery of C57BL/6 mice to establish a mouse acute myocardial infarction (AMI) model to observe changes in activated B cells and cytokines at different time points. Twelve-week-old C57BL/6 male mice were randomly divided into the Sham group (24 mice) (thread under the LAD artery without ligation) and the AMI group (64 mice). In addition, C57BL/6 B-cell knockout (BKO) mice and C57BL/6 wild-type (WT) mice were used to establish AMI models to observe the expression levels of cardiomyocyte cytokines, such as TNF-α IL-1β, IL-6, TGF-β1, COL1-A1, COL3-AIII, TIMP, and MMP9. Moreover, pathological and collagen changes in the myocardium were analysed. One-way ANOVA and LSD method was used for comparisons of multiple and pairwise groups respectively. P < 0.05 indicated significant differences. Results An AMI model of C57BL/6 mice was established successfully. The ratio of activated B cells and the expression of TNF-α, IL-1β, IL-6, TGF-β1, and B cell activating factor (BAFF) in the 5-day subgroup were the highest in the myocardium, spleen and peripheral blood with the most obvious myocardial inflammatory cell infiltration. The cytokines mRNA expression levels in the 5-day subgroup of the BKO group were decreased compared with those in the WT group (P < 0.05). Among the 2-week subgroups of the Sham, WT and BKO groups, the the LVEDd and LVESd of the BKO group were lower than those of the WT group (P < 0.05), and the left ventricular ejection fraction was higher than that of the WT group (P < 0.05). Conclusion Activated B cells participate in the sustained state of myocardial inflammation and immune system activation after AMI, and may affect the metabolism of myocardial collagen after AMI by secreting cytokines. Moreover, B cells promote the expression of myocardial collagen Type I and Type III and damage the left ventricular ejection function.

scholarly journals Are activated B cells involved in the process of myocardial fibrosis after acute myocardial infarction? -An in vivo experiment

2020 ◽  
Author(s):  
Fanrui Mo ◽  
Ying Luo ◽  
Yuluan Yan ◽  
Juan Li ◽  
Shayi Lai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
B Cells ◽  
Sham Group ◽  
Inflammatory Cells ◽  
Expression Levels ◽  
Tnf Α ◽  
Myocardial Collagen ◽  
Tgf Β1 ◽  
Activated B Cells

Abstract Background: Inflammatory cells infiltrate into the ischemic and hypoxic myocardial tissue after myocardial infarction. B cells gather at the site of myocardial injury and secrete cytokines to regulate immune inflammation and fiber repair processes.Methods: The animal experiment intended to use ligation of the left anterior descending branch of C57BL/6 mice to establish a mice AMI model to observe the changes of activated B cells and cytokines at different time points. 88 12-week-old C57BL/6 male mice were divided into the Sham group (24 mice) and acute myocardial infarction (AMI ) group (64 mice) randomly. Besides, C57BL/6 Bmi-1 knock out (BKO) mice and C57BL/6 wild-type (WT) mice were used to establish AMI models to observe the expression levels of cardiomyocyte factors including TNF-α and IL-1β, IL-6, TGF-β1, COL1-A1, COL3-A1, TIMP-1, and MMP9. Moreover, pathological and collagen changes in the myocardium were analyzed. One-way ANOVA analysis of variance was used for comparison between multiple groups, and the LSD method was used for pairwise comparison between groups. P < 0.05 indicated statistical differences.Results: AMI model of C57BL/6 mice was established successfully. The ratio of activated B cells and expression of TNF-α, IL-1β, IL-6, TGF-β1, and BAFF in 5 days subgroup was highest in the myocardium, spleen, and peripheral blood with the most obvious myocardial inflammatory cells infiltration. mRNA expression levels of TNF-α, IL-1β, IL-6, TGF-β1 in 5 days subgroup of the BKO group were decreased compared with the WT group (P < 0.05). Among 2 weeks subgroups of Sham, WT, and BKO groups, the LVEDd and LVESd in the BKO and WT groups were less than those in the Sham group (P < 0.05). The LVEDd and LVESd of the BKO group were less than the WT group,EF was higher than the WT group (P < 0.05).Conclusion: Activated B cells participated in the sustained state of myocardial inflammation and immune system activation after AMI via promoting the secretion of cytokines, and may affect the metabolism of myocardial collagen. Moreover, B cells could damage the heart structure and left ventricular ejection function by promoting the expression of myocardial collagen Type I and type III.

Randomized, double blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-MI: rationale, design and first interim analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Von Lewinski ◽  
B Merkely ◽  
I Buysschaert ◽  
R.A Schatz ◽  
G.G Nagy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Adverse Events ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Early Recovery ◽  
Ventricular Ejection Fraction ◽  
Combined Application

Abstract Background Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Mobilization of stem cells and homing within the infarcted area have been identified as the key mechanisms for successful treatment. Application of granulocyte-colony stimulating factor (G-CSF) is the least invasive way to mobilize stem cells while DDP4-inhibitor facilitates homing via stromal cell-derived factor 1 alpha (SDF-1α). Dutogliptin, a novel DPP4 inhibitor, combined with stem cell mobilization using G-CSF significantly improved survival and reduced infarct size in a murine model. Purpose We initiated a phase II, multicenter, randomized, placebo-controlled efficacy and safety study (N=140) analyzing the effect of combined application of G-CSF and dutogliptin, a small molecule DPP-IV-inhibitor for subcutaneous use after acute myocardial infarction. Methods The primary objective of the study is to evaluate the safety and tolerability of dutogliptin (14 days) in combination with filgrastim (5 days) in patients with STEMI (EF &lt;45%) following percutaneous coronary intervention (PCI). Preliminary efficacy will be analyzed using cardiac magnetic resonance imaging (cMRI) to detect &gt;3.8% improvement in left ventricular ejection fraction (LV-EF). 140 subjects will be randomized to filgrastim plus dutogliptin or matching placebos. Results Baseline characteristics of the first 26 patients randomized (24 treated) in this trial reveal a majority of male patients (70.8%) and a medium age of 58.4 years (37 to 84). During the 2-week active treatment period, 35 adverse events occurred in 13 patients, with 4 rated as serious (hospitalization due to pneumonia N=3, hospitalization due to acute myocardial infarction N=1), and 1 adverse event was rated as severe (fatal pneumonia), 9 moderate, and 25 as mild. 6 adverse events were considered possibly related to the study medication, including cases of increased hepatic enzymes (N=3), nausea (N=1), subcutaneous node/suffusion (N=1) and syncope (N=1). Conclusions Our data demonstrate that the combined application of dutogliptin and G-CSF appears to be safe on the short term and feasible after acute myocardial infarction and may represent a new therapeutic option in future. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This research is funded by the sponsor RECARDIO, Inc., 1 Market Street San Francisco, CA 94150, USA. RECARDIO Inc. is funding the complete study. The Scientific Board of RECARDIO designed the study. Data Collection is at the participating sites. Interpretation of the data by the Scientific Board and Manuscript written by the authors and approved by the Sponsor

Abstract 12691: Long-term Optimal Medical Therapy for Patients With Mid-range Left Ventricular Ejection Fraction After Acute Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
YeeKyoung KO ◽  
Seungjae JOO ◽  
Jong Wook Beom ◽  
Jae-Geun Lee ◽  
Joon-Hyouk CHOI ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Left Ventricular Ejection Fraction ◽  
Medical Therapy ◽  
Beta Blockers ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Ras Inhibitors

Introduction: In the era of the initial optimal interventional and medical therapy for acute myocardial infarction (AMI), a number of patients with mid-range left ventricular ejection fraction (40% <EF<50%) becomes increasing. However, the long-term optimal medical therapy for these patients has been rarely studied. Aims: This observational study aimed to investigate the association between the medical therapy with beta-blockers or inhibitors of renin-angiotensin system (RAS) and clinical outcomes in patients with mid-range EF after AMI. Methods: Among 13,624 patients enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), propensity-score matched patients who survived the initial attack and had mid-range EF were selected according to beta-blocker or RAS inhibitor therapy at discharge. Results: Patients with beta-blockers showed significantly lower 1-year cardiac death (2.4 vs. 5.2/100 patient-year; hazard ratio [HR] 0.46; 95% confidence interval [CI] 0.22-0.98; P =0.045) and MI (1.7 vs. 4.0/100 patient-year; HR 0.41; 95% CI 0.18-0.95; P =0.037). On the other hand, RAS inhibitors were associated with lower 1-year re-hospitalization due to heart failure (2.8 vs. 5.5/100 patient-year; HR 0.54; 95% CI 0.31-0.92; P =0.024), and no significant interaction with classes of RAS inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) was observed ( P for interaction=0.332). Conclusions: Beta-blockers or RAS inhibitors at discharge were associated with better 1-year clinical outcomes in patients with mid-range EF after AMI.

scholarly journals Acute myocardial infarction in young adults: features of pathogenesis, disease course and justification of strategy for prevention of complications

2019 ◽  
Vol 26 (4) ◽  
pp. 32-43
Author(s):  
O. M. Parkhomenko ◽  
Ya. M. Lutay ◽  
O. I. Irkin ◽  
D. O. Bilyi ◽  
A. O. Stepura ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Young Adults ◽  
Young Patients ◽  
Coronary Vessels ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Premature Coronary Artery Disease ◽  
Ventricular Ejection Fraction ◽  
Arrhythmogenic Substrate

We retrospectively and prospectively studied 835 patients with acute myocardial infarction (AMI) under the age of 45 and older. Depending on age, patients were divided into two groups: < 45 years and ≥ 45 years. In 189 patients under 45 years of age, the main risk factors leading to the development of ST-elevation myocardial infarction were male sex (OR 6.58; 95 % CI (2.64–16.41), smoking (OR 2.02; 95 % CI (1.44–2.82) and family history of premature coronary artery disease (OR 1.75; 95 % CI (1.21–2.54). According to coronary angiography, AMI patients under 45 years of age in most cases showed no hemodynamically significant coronary vessels damage and had a different course of AMI caused by other reasons – aneurysms of the coronary arteries, muscle bridges, coronary spasm, spontaneous dissections. It was found that 10 % of young patients who did not have obstructive lesions of coronary vessels, according to magnetic resonance imaging (MRI) had focal myocarditis. However, it is noted that in patients under 45 years of age, the presence of familial hypercholesterolemia (FH) may affect the development of AMI. Thus, according to the DLCNS criteria, FH was more frequently reported in young patients than in patients older than 45 years (7.34 % vs 1.32 % (p<0.05)). Hospital course of AMI in young adults was more favorable, with fewer complications. Data from studies of flow-dependent vasodilation have shown that young patients have worse endothelial function on the 1st day of AMI (p=0.043), but better recovery of it in the dynamics of observation. However, in young patients, early (day 7, p=0.029) and late (day 90, p=0.041) left ventricular dilatation was more commonly reported compared with older patients. According to the MRI data on day 1 and in the dynamics (90 days), it was found that, despite the higher prevalence of AMI, young patients have better recovery of contractile myocardial function. The arrhythmogenic substrate (according to late ventricular potential) for life-threatening arrhythmias was more commonly recorded in the older age group at the beginning of the development of AMI, but it was detected with the same frequency in both groups during prolonged observation (6–12 months). Despite better survival and fewer complications during long-term follow-up (4.9 years on average), the greatest impact on the development of the combined endpoint (cardiovascular death / recurrent myocardial infarction / stroke) and death from any cause was made by the patients’ age up to 35 years (best prognosis), concomitant hypertension (worsens prognosis) and low left ventricular ejection fraction (increases complications). The study indicates the possibility of implementing a secondary prevention system in AMI patients of young age through careful (active) observation and control of adherence to treatment and the adequacy of its implementation.

Sign in / Sign up

Export Citation Format

Share Document