Abstract 362: Acute Exposure to Air Pollution Aggravates Acute Myocardial Infarction and Subsequent Ischemic Heart Failure in Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Dennis Wolf ◽  
Timoteo Marchini ◽  
Nathaly Anto Michel ◽  
Daniel Dürschmied ◽  
Ingo Hilgendorf ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Air Pollution ◽  
Endothelial Cells ◽  
Particulate Matter ◽  
Alveolar Macrophages ◽  
Intravital Microscopy ◽  
Ischemic Heart Failure ◽  
Cell Recruitment ◽  
Tnf Α

Background: Clinical, but not experimental evidence has suggested that exposure to air pollution particulate matter (PM) aggravates myocardial infarction (MI) in humans. Here, we aimed to describe mechanisms and consequences of an acute PM exposure in an experimental mouse model of MI. Methods and Results: C57BL/6J mice were exposed to an air pollution particulate matter (PM) surrogate (Residual Oil Fly Ash) by intranasal installation, prior to surgical permanent ligation of the left anterior descending coronary artery (LAD). Mice exposed to PM showed exaggerated ischemic heart failure with decreased fractional shortening and diastolic dilatation in echocardiography 6 month after MI. Histological analysis demonstrated an increase in the infarct area by 45 ± 12 % and enhanced inflammatory cell recruitment into the myocardium of PM-exposed mice 6 days after MI. Augmented cell recruitment was caused by increased activation of circulating myeloid and vascular endothelial cells. Consistently, PM exposure increased leukocyte recruitment a model of sterile peritonitis and in intravital microscopy. Mechanistically, PM exposure potentiated levels of circulating pro-inflammatory cytokines, such as of TNF-α by up to 327 ± 100 %. Increased activation of endothelial cells and leukocytes could be reversed by TNF-α antibody blockade. We identified alveolar macrophages as primary source of elevated cytokine production. Accordingly, specific in vivo depletion of lung macrophages by clodronate inhibited cytokine secretion, abolished leukocyte recruitment in intravital microscopy, and protected from cardiac inflammation after simultaneous PM exposure. Conversely, lymphocyte-free Rag1 -/- mice where susceptible to PM, indicating that alveolar macrophages, but not lymphocytes, are the cause of the systemic inflammatory response following air pollution. Conclusion: Our data demonstrate that an acute exposure to environmental PM worsens MI and its clinical outcome in mice. These findings provide a novel functional link between air pollution and inflammatory pathways, and emphasize the importance of environmental factors in cardiovascular disease.

scholarly journals ACE Inhibition Modulates Myeloid Hematopoiesis after Acute Myocardial Infarction and Reduces Cardiac and Vascular Inflammation in Ischemic Heart Failure

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 396
Author(s):  
Wolf-Stephan Rudi ◽  
Michael Molitor ◽  
Venkata Garlapati ◽  
Stefanie Finger ◽  
Johannes Wild ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Bone Marrow ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Vascular Inflammation ◽  
Ace Inhibition ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Ischemic Heart Failure

Aims: Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a cornerstone of drug therapy after myocardial infarction (MI) and improve left ventricular function and survival. We aimed to elucidate the impact of early treatment with the ACE inhibitor ramipril on the hematopoietic response after MI, as well as on the chronic systemic and vascular inflammation. Methods and Results: In a mouse model of MI, induced by permanent ligation of the left anterior descending artery, immediate initiation of treatment with ramipril (10 mg/k/d via drinking water) reduced cardiac inflammation and the number of circulating inflammatory monocytes, whereas left ventricular function was not altered significantly, respectively. This effect was accompanied by enhanced retention of hematopoietic stem cells, Lin−Sca1−c-Kit+CD34+CD16/32+ granulocyte–macrophage progenitors (GMP) and Lin−Sca1−c-Kit+CD150−CD48− multipotent progenitors (MPP) in the bone marrow, with an upregulation of the niche factors Angiopoetin 1 and Kitl at 7 d post MI. Long-term ACE inhibition for 28 d limited vascular inflammation, particularly the infiltration of Ly6Chigh monocytes/macrophages, and reduced superoxide formation, resulting in improved endothelial function in mice with ischemic heart failure. Conclusion: ACE inhibition modulates the myeloid inflammatory response after MI due to the retention of myeloid precursor cells in their bone marrow reservoir. This results in a reduction in cardiac and vascular inflammation with improvement in survival after MI.

Abstract P391: Inhalation Of Airborne Particulate Matter Alters Cardiovascular Function Of Alzheimer-prone Mice

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Devin R O'Piela ◽  
Ty A Saldana ◽  
David M Aslaner ◽  
Matthew W Gorr ◽  
Amy R Mackos ◽  
...  
Keyword(s):  
Heart Failure ◽  
Air Pollution ◽  
Risk Factor ◽  
Particulate Matter ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Airborne Particulate Matter ◽  
Transgenic Mouse Model ◽  
Cardiovascular Dysfunction ◽  
Airborne Particulate

Air pollution has detrimental effects on cardiovascular and lung function, and the extent of its pathological consequences continues to be uncovered. Recently, air pollution has been implicated in the development of Alzheimer Disease (AD) progression. AD and heart failure are common co-morbidities, giving reason to believe that cardiovascular dysfunction may contribute to AD. A known contributor to cardiovascular dysfunction-particulate matter (PM 2.5 , < 2.5 μm diameter)—is a critical component of air pollution and is considered a risk factor for heart failure and AD development. This co-morbidity pattern and shared environmental risk factor prompted the hypothesis that PM 2.5 contributes to cardiovascular dysfunction in a transgenic mouse model of AD. We tested our hypothesis by subjecting 6-month-old transgenic (APP) and non-carrier wildtype (WT) male mice to filtered air (FA) or PM 2.5 for 5 days/week, 6 hours/day for 3 months (n = 34). Following exposure, echocardiography, pressure-volume (PV) loops, and respiratory mechanics were performed to detect cardiac and pulmonary changes associated with genotype and exposure conditions among the 3-month group. Echocardiography revealed left ventricular anterior wall thickness in systole was significantly elevated among PM-exposed APP mice compared to FA-exposed APP controls. PV data demonstrated significant reduced end-systolic elastance in PM-exposed mice compared to FA-exposed mice in both WT and APP mouse models, demonstrating impaired contractility. PV loops also showed that the time constant of isovolumetric relaxation was increased in PM-exposed compared to FA-exposed WT mice. APP mice experienced higher lung resistance and central airway resistance with an increasing dose of methacholine. Taken together, these findings indicate airborne particulate matter exposure causes cardiac and pulmonary dysfunction in a transgenic mouse model of AD.

Cumulative exposure to particulate matter air pollution and long-term post-myocardial infarction outcomes

2013 ◽  
Vol 57 (4) ◽  
pp. 339-344 ◽  
Author(s):  
Silvia Koton ◽  
Noa Molshatzki ◽  
Yuval ◽  
Vicki Myers ◽  
David M. Broday ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Air Pollution ◽  
Particulate Matter ◽  
Post Myocardial Infarction ◽  
Cumulative Exposure

scholarly journals Long‐Term Exposure to Particulate Air Pollution Is Associated With 30‐Day Readmissions and Hospital Visits Among Patients With Heart Failure

2021 ◽  
Author(s):  
Cavin K. Ward‐Caviness, ◽  
Mahdieh Danesh Yazdi, ◽  
Joshua Moyer, ◽  
Anne M. Weaver, ◽  
Wayne E. Cascio, ◽  
...  
Keyword(s):  
Heart Failure ◽  
Air Pollution ◽  
Particulate Matter ◽  
Fine Particulate Matter ◽  
Total Hospital ◽  
Fine Particulate ◽  
Patients With Heart Failure ◽  
Hospital Visits ◽  
Pollution Exposure

Background Long‐term air pollution exposure is a significant risk factor for inpatient hospital admissions in the general population. However, we lack information on whether long‐term air pollution exposure is a risk factor for hospital readmissions, particularly in individuals with elevated readmission rates. Methods and Results We determined the number of readmissions and total hospital visits (outpatient visits+emergency room visits+inpatient admissions) for 20 920 individuals with heart failure. We used quasi‐Poisson regression models to associate annual average fine particulate matter at the date of heart failure diagnosis with the number of hospital visits and 30‐day readmissions. We used inverse probability weights to balance the distribution of confounders and adjust for the competing risk of death. Models were adjusted for age, race, sex, smoking status, urbanicity, year of diagnosis, short‐term fine particulate matter exposure, comorbid disease, and socioeconomic status. A 1‐µg/m 3 increase in fine particulate matter was associated with a 9.31% increase (95% CI, 7.85%–10.8%) in total hospital visits, a 4.35% increase (95% CI, 1.12%–7.68%) in inpatient admissions, and a 14.2% increase (95% CI, 8.41%–20.2%) in 30‐day readmissions. Associations were robust to different modeling approaches. Conclusions These results highlight the potential for air pollution to play a role in hospital use, particularly hospital visits and readmissions. Given the elevated frequency of hospitalizations and readmissions among patients with heart failure, these results also represent an important insight into modifiable environmental risk factors that may improve outcomes and reduce hospital use among patients with heart failure.

scholarly journals The risk of admission acute heart failure in ST-elevation myocardial infarction patients and air pollution with PM2.5

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Sinkovic ◽  
M Krasevec ◽  
D Suran ◽  
M Marinsek ◽  
A Markota
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Air Pollution ◽  
Acute Heart Failure ◽  
St Elevation Myocardial Infarction ◽  
Vascular Events ◽  
Limit Values ◽  
Predictive Role ◽  
St Elevation

Abstract Introduction Air pollution, in particular exposure to particulate matter fine particles of less than 2.5 microns in diameter (PM2.5), increases the risk of cardiovascular events. Short-term exposure (hours to few days prior) to increased PM2.5 levels even may help trigger ST-elevation myocardial infarction (STEMI) and heart failure exacerbation in susceptible individuals. The risk of vascular events is increased even in exposures below the current European air quality limit values (mean annual levels for PM2.5 less than 10μg/m3, 24-hour mean level less than 25μg/m3). Purpose To evaluate predictive role of PM2.5 levels ≥20 μg/m3 one day prior to hospital admission for the risk of admission acute heart failure (AAHF) in STEMI patients. Methods In 290 STEMI patients (100 women, 190 men, mean age 65.5±12.9 years), treated by primary percutaneous coronary intervention (PPCI) in 2018, we retrospectively registered the AAHF, defined as classes II-IV by Killip Kimbal classification. Additionally, we registered admission clinical data, potentially contributing to AAHF in STEMI patients such as gender, age ≥65 years, prior resuscitation, admission cTnI ≥5 μg/L (normal levels up to 0.045 μg/L), comorbidities, time to PPCI, and mean daily levels of PM2.5 ≥20 μg/m3 one day before admission. Mean daily, freely available, levels of PM2.5 were measured and registered by Chemical analytic laboratory of Environmental agency of Republic Slovenia. We evaluated the predictive role of admission data for admission AHF in STEMI patients. Results AAHF was observed in 34.5% of STEMI patients with the mean daily PM2.5 level 15.7±10.9 μg/m3 on the day before admission. PPCI was performed in 92.1% of all STEMI patients, in AAHF in 87.1% and in non-AAHF patients in 94.7% (p=0.037). AAHF in comparison to non-AAHF was associated significantly with female gender (50.5% vs 25.9%, p&lt;0.001), age over 65 years (71.3% vs 45%, p&lt;0.001), prior diabetes (33.7% vs 14.8%, p&lt;0.001), left bundle branch block (LBBB) (10.9% vs 0.5%, &lt;0.001), admission cTnI ≥5 μg/L (46.7% vs 25.9%, p&lt;0.001) and mean daily levels of PM2.5 ≥20 μg/m3 one day before admission (31.7% vs 19%, p=0.020), but nonsignificantly with arterial hypertension, prior myocardial infarction, anterior STEMI and time to PPCI. Logistic regression demonstrated that significant independent predictors of AAHF were age over 65 years (OR 3.349, 95% CI 1.787 to 6.277, p&lt;0.001), prior diabetes (OR 2.934, 95% CI 1.478 to 5.821, p=0.002), admission LBBB (OR 10.526, 95% CI 1.181 to 93.787, p=0.03), prior resuscitation (OR 3.221, 95% CI 1.336 to 7.761, p=0.009), admission cTnI ≥5μg/l (OR 2.984, 95% CI 1.618 to 5.502, p&lt;0.001) and mean daily levels of PM2.5 ≥20 μg/m3 (OR 2.096, 95% CI 1.045 to 4.218, p=0.038) one day before admission. Conclusion Mean daily levels of PM2.5 ≥20μg/m3 one day before admission were among significant independent predictors of AAHF in STEMI patients. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Generation of Cardiomyocytes From Vascular Adventitia-Resident Stem Cells

2018 ◽  
Vol 123 (6) ◽  
pp. 686-699 ◽  
Author(s):  
Subba Rao Mekala ◽  
Philipp Wörsdörfer ◽  
Jochen Bauer ◽  
Olga Stoll ◽  
Nicole Wagner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Stem Cells ◽  
Endothelial Cells ◽  
Aortic Wall ◽  
Fluorescent Protein ◽  
Therapeutic Option ◽  
Cardiac Regeneration ◽  
Cardiac Progenitors ◽  
Resident Stem Cells

Rationale: Regeneration of lost cardiomyocytes is a fundamental unresolved problem leading to heart failure. Despite several strategies developed from intensive studies performed in the past decades, endogenous regeneration of heart tissue is still limited and presents a big challenge that needs to be overcome to serve as a successful therapeutic option for myocardial infarction. Objective: One of the essential prerequisites for cardiac regeneration is the identification of endogenous cardiomyocyte progenitors and their niche that can be targeted by new therapeutic approaches. In this context, we hypothesized that the vascular wall, which was shown to harbor different types of stem and progenitor cells, might serve as a source for cardiac progenitors. Methods and Results: We describe generation of spontaneously beating mouse aortic wall-derived cardiomyocytes without any genetic manipulation. Using aortic wall-derived cells (AoCs) of WT (wild type), αMHC (α-myosin heavy chain), and Flk1 (fetal liver kinase 1)-reporter mice and magnetic bead-associated cell sorting sorting of Flk1 + AoCs from GFP (green fluorescent protein) mice, we identified Flk1 + CD (cluster of differentiation) 34 + Sca-1 (stem cell antigen-1)-CD44 − AoCs as the population that gives rise to aortic wall-derived cardiomyocytes. This AoC subpopulation delivered also endothelial cells and macrophages with a particular accumulation within the aortic wall-derived cardiomyocyte containing colonies. In vivo, cardiomyocyte differentiation capacity was studied by implantation of fluorescently labeled AoCs into chick embryonic heart. These cells acquired cardiomyocyte-like phenotype as shown by αSRA (α-sarcomeric actinin) expression. Furthermore, coronary adventitial Flk1 + and CD34 + cells proliferated, migrated into the myocardium after mouse myocardial infarction, and expressed Isl-1 + (insulin gene enhancer protein-1) indicative of cardiovascular progenitor potential. Conclusions: Our data suggest Flk1 + CD34 + vascular adventitia-resident stem cells, including those of coronary adventitia, as a novel endogenous source for generating cardiomyocytes. This process is essentially supported by endothelial cells and macrophages. In summary, the therapeutic manipulation of coronary adventitia-resident cardiac stem and their supportive cells may open new avenues for promoting cardiac regeneration and repair after myocardial infarction and for preventing heart failure.

Abstract 15149: Short-term Exposure to Fine Particulate Matter Air Pollution Preferentially Increases the Risk of ST-Elevation Acute Coronary Events

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kent G Meredith ◽  
C A Pope ◽  
Joseph B Muhlestein ◽  
Jeffrey L Anderson ◽  
John B Cannon ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Air Pollution ◽  
Particulate Matter ◽  
Fine Particulate Matter ◽  
Significant Coronary Artery Disease ◽  
St Elevation Myocardial Infarction ◽  
Short Term ◽  
Fine Particulate ◽  
Short Term Exposure ◽  
St Elevation

Introduction: Air pollution is associated with greater cardiovascular event risk, but which types of events and the specific at-risk individuals remain unknown. Hypothesis: Short-term exposure to fine particulate matter (PM 2.5 ) is associated with greater risk of acute coronary syndromes (ACS), including ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (USA). Methods: ACS events treated at Intermountain Healthcare hospitals in Utah’s urban Wasatch Front region between September 10, 1993 and May 15, 2014 were included if the patient resided in that area (N=16,314). A time-stratified case-crossover design was performed matching the PM 2.5 exposure at the time of event with periods when the event did not occur (referent), for STEMI, NSTEMI, and USA. Patients served as their own controls. Odds ratios (OR) were determined for exposure threshold versus linear, non-threshold models. Results: In STEMI, NSTEMI, and USA patients, age averaged 62, 64, and 63 years; males constituted 73%, 66%, and 68%; current or past smoking was prevalent in 33%, 25%, and 26%; and significant coronary artery disease (CAD) (defined as ≥1 coronary with ≥70% stenosis) was found among 95%, 75%, and 74%, respectively. Short-term PM 2.5 exposure was associated with ACS events (Table). Conclusions: Short-term exposure of PM 2.5 was strongly associated with greater risk of STEMI, especially in patients with angiographic CAD. No association with NSTEMI was found, and only a weak effect for USA. This study supports a PM 2.5 exposure threshold of 25 μg/m 3 , below which little exposure effect is seen, while the effect is linear above that level.

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