MicroRNA 21 and Hypoxia Inducible Factor 1 coordinate the impact of B lymphocytes on cardiac function after acute myocardial infarction

Abstract Background Myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Mature B lymphocytes have been shown to exacerbate tissue injury and deterioration of cardiac function after MI. However, the cellular and molecular mechanisms governing B cell deleterious effects in the ischemic milieu remain to be defined. Purpose In this study, we speculate that endogenous activation of the miR21/HIFα-related pathways mediates the effect of B lymphocytes on post-ischemic cardiac remodeling. Methods Acute MI was induced by permanent ligation of the left anterior descending artery in mice. Cardiac function and remodeling was determined by echocardiography and immunohistochemistry. Inflammatory cell number and phenotype were defined by FACS analysis. To evaluate the role of HIFα isoforms in B cells, we generated mice with B cell lineage specific (Cd79aCre/+) conditional deletion of HIF1α (HIF1αflox/flox), HIF2α (HIF2αflox/flox), or both isoforms (HIF1α-HIF2αflox/flox). Results Acute MI increased miR21 levels in B cells. miR21 deficient mice showed reduced B cell numbers in the spleen, blood and subsequently in the injured cardiac tissue. Transplantation of bone marrow derived cells isolated from miR21-deficient mice (miR21−/−) improved cardiac function and remodeling when compared to administration of wild-type (WT) bone marrow cells. Similarly, in Rag1−/− immunodeficient mice with acute MI, re-supplementation with miR21−/− B lymphocytes restored cardiac repair and function when compared to injection of WT B cells. miR21 abrogated PTEN contents and subsequently enhanced HIF1α levels in cultured B cells. B cell deletion of HIF1α, but not that of HIF2α, reduced B cell accumulation and improved cardiac function after MI. Mice, which were equally deficient in HIF1α and HIF2α, also exhibited abrogation of adverse ventricular remodeling and showed recovery of cardiac function after MI. Toll like receptor agonist, CpG, fostered the release of the monocyte chemo-attractant protein, Ccl7, in cultured WT B cells but not in miR21- or HIF1α- deficient B cells. Ccl7 circulating levels were also reduced in miR21−/− and Cd79aCre/+/HIF1α flox/flox animals after acute MI. Ccl7 down-regulation hampered Ly6Chigh monocyte infiltration in the ischemic myocardium, leading to decreased infarct size and interstitial fibrosis, supporting cardiac repair. Conclusion This work reveals a novel function for miR21/HIF1α related pathways in B lymphocyte dependent effect on cardiac function and remodeling in the setting of acute MI.

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Correction to: The impact of epicardial adipose tissue in patients with acute myocardial infarction

Clinical Research in Cardiology ◽

10.1007/s00392-021-01889-w ◽

2021 ◽

Author(s):

Christoph Fisser ◽

Stefan Colling ◽

Kurt Debl ◽

Andrea Hetzenecker ◽

Ulrich Sterz ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Adipose Tissue ◽

Epicardial Adipose Tissue ◽

The Impact

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Impact of COVID-19 pandemic lockdown on myocardial infarction care

European Journal of Epidemiology ◽

10.1007/s10654-021-00764-2 ◽

2021 ◽

Author(s):

Timo Schmitz ◽

Christa Meisinger ◽

Inge Kirchberger ◽

Christian Thilo ◽

Ute Amann ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Hot Spot ◽

Population Based ◽

Downward Trend ◽

German Model ◽

Model Region ◽

The Impact ◽

The City

AbstractThe aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors in the German model region for complete AMI registration. The analysis was based on data from the population-based KORA Myocardial Infarction Registry located in the region of Augsburg, Germany. All cases of AMI (n = 210) admitted to one of four hospitals in the city of Augsburg or the county of Augsburg from February 10th, 2020, to May 19, 2020, were included. Patients were divided into three groups, namely pre-lockdown, strict lockdown, and attenuated lockdown period. An additional survey was conducted asking the patients for stress and fears in the 4 weeks prior to their AMI. The AMI rate declined by 44% in the strict lockdown period; in the attenuated lockdown period the rate was 17% lower compared to the pre-lockdown period. The downward trend in AMI rates during lockdown was seen in STEMI and NSTEMI patients, and independent of sex and age. The door-to-device time decreased by 70–80% in the lockdown-periods. In the time prior to the infarction, patients felt stressed mainly due to fear of infection with Sars-CoV-2 and less because of the restrictions and consequences of the lockdown. A strict lockdown due to the Covid-19 pandemic had a marked impact on AMI care even in a non-hot-spot region with relatively few cases of COVID-19. Fear of infection with the virus is presumably the main reason for the drop in hospitalizations due to AMI.

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Sample Timing, Diagnosis of Subclinical Thyroid Dysfunction and Mortality in Acute Myocardial Infarction: ThyrAMI1 Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz143 ◽

2019 ◽

Vol 105 (4) ◽

pp. e1299-e1306 ◽

Cited By ~ 3

Author(s):

Salman Razvi ◽

Owain Leng ◽

Avais Jabbar ◽

Arjola Bano ◽

Lorna Ingoe ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Thyroid Function ◽

Thyroid Dysfunction ◽

Reference Interval ◽

Reference Ranges ◽

Diagnosis And Prognosis ◽

Time Period ◽

All Cause Mortality ◽

The Impact

Abstract Objective The objective of this study was to determine the impact of blood sample timing on the diagnosis of subclinical thyroid dysfunction (SCTD) and mortality in patients with acute myocardial infarction (AMI). Patients, Design, and Main Outcome Measures Patients with AMI had thyroid function evaluated on admission between December 2014 and December 2016 and those with abnormal serum thyrotropin (TSH) had repeat thyroid function assessed at least a week later. The association between sample timing and SCTD was evaluated by logistic regression analysis. Secondary outcomes were confirmation of SCTD on repeat testing and all-cause mortality up to June 2018. Results Of the 1806 patients [29.2% women, mean (± standard deviation) age of 64.2 (±12.1) years] analyzed, the prevalence of subclinical hypothyroidism (SCH) was 17.2% (n = 311) and subclinical hyperthyroidism (SHyper) was 1.2% (n = 22) using a uniform TSH reference interval. The risk of being diagnosed with SCTD varied by sample timing in fully-adjusted models. The risk of SCH was highest between 00.01 and 06.00 hours and lowest between 12.01 and 18.00 hours, P for trend <.001, and risk of SHyper was highest between 12.01 hours and 18.00 hours and lowest between 00.01 hours and 06.00 hours. Furthermore, time of the initial sample was associated with the risk of remaining in a SCH state subsequently. Mortality in SCH patients was not elevated when a uniform TSH reference interval was utilized. However, when time period–specific TSH reference ranges were utilized, the mortality risk was significantly higher in SCH patients with HR (95% CI) of 2.26 (1.01–5.19), P = .04. Conclusions Sample timing impacts on the diagnosis and prognosis of SCH in AMI patients. If sample timing is not accounted for, SCH is systemically misclassified, and its measurable influence on mortality is lost.

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Primary care physician services and the frequency of comorbidities in patients with acute myocardial infarction

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.265 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

R King ◽

D Giedrimiene

Keyword(s):

Myocardial Infarction ◽

Primary Care ◽

Acute Myocardial Infarction ◽

Primary Care Physician ◽

Care Physician ◽

Adverse Outcomes ◽

Coronary Syndrome ◽

Number Of Patients ◽

Significant Difference ◽

The Impact

Abstract Funding Acknowledgements Type of funding sources: None. Background The management of patients with multiple comorbidities represents a significant burden on healthcare each year. Despite requiring regular medical care to treat chronic conditions, a large number of these patients may not receive proper care. Significant disparities have been identified in patients with multiple comorbidities and those who experience acute coronary syndrome or acute myocardial infarction (AMI). Only limited data exists to identify the impact of comorbidities and utilization of primary care physician (PCP) services on the development of adverse outcomes, such as AMI. Purpose The primary objective was to analyze how PCP services utilization can be associated with comorbidities in patients who experienced an AMI. Methods This study was based on retrospective data analysis which included 250 patients admitted to the Hartford Hospital Emergency Department (ED) for an AMI. Out of these, 27 patients were excluded due to missing documentation. Collected data included age, gender, medications and recorded comorbidities, such as hypertension, hyperlipidemia, diabetes mellitus (DM), chronic kidney disease (CKD) and previous arrhythmia. Each patient was assessed regarding utilization of PCP services. Statistical analysis was performed in order to identify differences between patients with documented PCP services and those without by using the Chi-square test. Results The records allowed for identification of documented PCP services for 172 out of 223 (77.1%) patients. The most common comorbidities were hypertension and hyperlipidemia: in 165 (74.0%) and 157 (70.4%) cases respectively. The most frequent comorbidity was hypertension: 137 out of 172 (79.7%) in pts with PCP vs 28 out of 51 (54.9%) without PCP, and significantly more often in patients with PCP, p< 0.001. Hyperlipidemia was the second most frequent comorbidity: in 130 out of 172 (75.6%) vs 27 out of 51 (52.9%) accordingly, and also significantly more often (p< 0.002) in patients with PCP services. The number of comorbidities ranged from 0-5, including 32 (14.3%) patients without comorbidities: 16 (9.3%) with a PCP and 16 (31.4%) without PCP services. The majority of patients - 108 (48.5% of 223), had 2-3 documented comorbidities: 89 (51.8%) had two and 19 (34.6%) had three. The remaining 40 (17.9%) patients had 4-5 comorbidities: 37 (21.5%) of them with a PCP and 3 (10.3%) without, with a significant difference (p < 0.001) found for patients with a higher number of comorbidities who utilized PCP services. Conclusions Our study shows that the majority of patients who presented with an AMI had one or more comorbidities. Furthermore, patients who did not utilize PCP services had fewer identified comorbidities. This suggests that there may be a significant number of patients who experienced AMI with undiagnosed comorbidities due to not having access to PCP services.

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