scholarly journals Role of P2X purinergic receptors in the rescue of ischemic heart failure

2008 ◽  
Vol 295 (3) ◽  
pp. H1191-H1197 ◽  
Author(s):  
Dmitry Sonin ◽  
Si-Yuan Zhou ◽  
Chunxia Cronin ◽  
Tatiana Sonina ◽  
Jeffrey Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Infarct Size ◽  
Purinergic Receptors ◽  
P2x Receptors ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Post Myocardial Infarction ◽  
Ischemic Heart Failure

Evidence is accumulating to support the presence of P2X purinergic receptors in the heart. However, the biological role of this receptor remains to be defined. The objectives here were to determine the role of cardiac P2X receptors in modulating the progression of post-myocardial infarction ischemic heart failure and to investigate the underlying mechanism. The P2X4 receptor (P2X4R) is an important subunit of native cardiac P2X receptors, and the cardiac-specific transgenic overexpression of P2X4R (Tg) was developed as a model. Left anterior descending artery ligation resulted in similar infarct size between Tg and wild-type (WT) mice ( P > 0.1). However, Tg mice showed an enhanced cardiac contractile performance at 7 days, 1 mo, and 2 mo after infarction and an increased survival at 1 and 2 mo after infarction ( P < 0.01). The enhanced intact heart function was manifested by a greater global left ventricular developed pressure and rate of contraction of left ventricular pressure in vitro and by a significantly increased fractional shortening and systolic thickening in the noninfarcted region in vivo ( P < 0.05). The salutary effects on the ischemic heart failure phenotype were seen in both sexes and were not the result of any difference in infarct size in Tg versus WT hearts. An enhanced contractile function of the noninfarcted area in the Tg heart was likely an important rescuing mechanism. The cardiac P2X receptor is a novel target to treat post-myocardial infarction ischemic heart failure.

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 250: Differential Role of Autophagy in Idiopathic versus Ischemic Heart Failure in Humans

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Antoinette Bugyei-Twum ◽  
Krishna K Singh ◽  
Filio Billia ◽  
Kim A Connelly
Keyword(s):  
Heart Failure ◽  
Ischemia Reperfusion ◽  
Fold Increase ◽  
Left Ventricular ◽  
Beclin 1 ◽  
Ischemic Heart ◽  
Autophagic Flux ◽  
Ischemic Heart Failure ◽  
Autophagic Activity

Background: Autophagy is an evolutionary conserved process that plays a key role in a variety of physiological and pathological processes. Despite its beneficial role, excessive/insufficient autophagic activity is known to contribute to the pathogenesis of cardiovascular disorders, including ischemia/reperfusion injury and heart failure. However, the differential role of autophagy in idiopathic versus ischemic heart failure remains unknown. Methods: To investigate the role of autophagy and associated apoptosis in idiopathic versus ischemic heart failure, we obtained LV myocardium biopsies from healthy controls (via 3 commercial sources), and from 10 patients with idiopathic and ischemic end-stage heart failure before the insertion of a left ventricular assist devise. The expression of inducers/markers of autophagy (mTOR, phospho-mTOR, LC3-I/II, p62, Beclin-1, autophagy-related genes ATG4B/ATG5) and apoptosis (Bcl-2 and caspase-3) were assessed at the transcript and protein level using quantitative RT-PCR and Western blotting. Results: Autophagy was activated in both idiopathic and ischemic heart failure in comparison to control, as confirmed by a significant reduction in mTOR expression/activation and a 3.4-fold and 2.2-fold increase in LC3 II/I ratio, respectively. An increase in apoptosis, marked by increased caspase3 and Bcl2 expression, was also observed in both groups in comparison to control. Interestingly, autophagy activity—marked by decreased mTOR expression/activation, increased ATG4B, ATG5, and Beclin-1—was significantly higher in idiopathic heart failure, when compared to ischemic heart failure. While we observed increased autophagic activity in idiopathic heart failure, p62 expression was also significantly increased in this group (2.8-fold increase; p<0.05), demonstrating an impairment of autophagic flux in idiopathic versus ischemic heart failure. Conclusions: For the first time, we provide a direct comparision of autophagy and apoptosis in idiopathic versus ischemic heart failure. Our data, demonstrating an excessive yet insufficient autophagic activity in idiopathic heart failure, suggests a differential role of autophagy apoptosis in idiopathic versus ischemia-related heart failure.

scholarly journals Post-myocardial infarction heart failure dysregulates the bone vascular niche

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jedrzej Hoffmann ◽  
Guillermo Luxán ◽  
Wesley Tyler Abplanalp ◽  
Simone-Franziska Glaser ◽  
Tina Rasper ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Vascular Function ◽  
Ischemic Heart ◽  
Post Myocardial Infarction ◽  
Ischemic Heart Failure ◽  
Single Cell Rna Sequencing ◽  
Bone Vasculature ◽  
Infarction Heart ◽  
Age Independent

AbstractThe regulation of bone vasculature by chronic diseases, such as heart failure is unknown. Here, we describe the effects of myocardial infarction and post-infarction heart failure on the bone vascular cell composition. We demonstrate an age-independent loss of type H endothelium in heart failure after myocardial infarction in both mice and humans. Using single-cell RNA sequencing, we delineate the transcriptional heterogeneity of human bone marrow endothelium, showing increased expression of inflammatory genes, including IL1B and MYC, in ischemic heart failure. Endothelial-specific overexpression of MYC was sufficient to induce type H bone endothelial cells, whereas inhibition of NLRP3-dependent IL-1β production partially prevented the post-myocardial infarction loss of type H vasculature in mice. These results provide a rationale for using anti-inflammatory therapies to prevent or reverse the deterioration of bone vascular function in ischemic heart disease.

Clinical significance of chitotriosidase in outpatients with advanced heart failure

2020 ◽  
pp. jim-2020-001595
Author(s):  
Sara Cetin Sanlialp ◽  
Gokay Nar ◽  
Hande Senol
Keyword(s):  
Heart Failure ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Left Ventricular Ejection ◽  
Ischemic Heart Failure ◽  
Elisa Method ◽  
Ventricular Ejection Fraction ◽  
Diagnosis And Prognosis ◽  
The Relationship

The previous studies have shown that plasma chitotriosidase (CHIT) levels increase in many diseases with inflammation. However, there are no reported studies investigating the relationship between CHIT and chronic heart failure (CHF) which is an inflammatory process. Therefore, we aimed to investigate the role of CHIT in diagnosis and severity of CHF in this study. 36 patients (50% male, mean age 63.17±10.18 years) with left ventricular ejection fraction <40% and 27 controls (44% male, mean age 61.33±8.73 years) were included in this study. Patients with CHF were divided into two groups as ischemic heart failure (IHF) and non-ischemic heart failure (NIHF) according to the underlying etiology. Plasma CHIT and N-terminal pro brain natriuretic peptide (NT-proBNP) levels were measured by ELISA method. Plasma CHIT and NT-proBNP levels were higher in patients with CHF than in controls (CHIT 931.25±461.39 ng/mL, 232.79±61.28 ng/mL, p<0.001; NT-proBNP, 595.31±428.11 pg/mL vs 78.13±30.47 pg/L; p<0.001). Also, the levels of these parameters increased in IHF compared with NIHF (CHIT, 1139.28±495.22 ng/mL, 671.22±237.21 ng/mL, p=0.002; NT-proBNP, 792.87±461.26 pg/mL vs 348.36±202.61 pg/mL, p=0.001) and there was a strong correlation between NT-proBNP and CHIT (r=0.969, p<0.001). According to this study findings, plasma CHIT level increases in CHF and its increased levels are correlated with NT-proBNP which is used diagnosis and prognosis of HF.

scholarly journals Hydrogen Sulfide Therapy Suppresses Cofilin-2 and Attenuates Ischemic Heart Failure in a Mouse Model of Myocardial Infarction

2020 ◽  
Vol 25 (5) ◽  
pp. 472-483
Author(s):  
Khoa Nguyen ◽  
Vinh Q. Chau ◽  
Adolfo G. Mauro ◽  
David Durrant ◽  
Stefano Toldo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Hydrogen Sulfide ◽  
Saline Group ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Saline Control ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Ischemic Heart Failure

Aims: Hydrogen sulfide (H2S) protects against ischemic and inflammatory injury following myocardial ischemia via induction of microRNA (miR)-21. We sought to determine whether H2S attenuates ischemic heart failure with reduced ejection fraction (HFrEF) and interrogate the role of cofilin-2, a target of miR-21, in this protective process. Methods and Results: Adult male mice underwent myocardial infarction (MI) by coronary artery ligation after baseline echocardiography. Following MI, mice were treated with Na2S (100 μg/kg/day; intraperitoneal [IP]) or saline up to 28 days. End-diastolic pressure, measured by Millar catheter, was significantly increased ( P < .05 vs sham) at 3 days post-MI in the saline group, which was attenuated with Na2S. Left ventricular (LV) fractional shortening decreased significantly at 28 days post-MI in the saline group but was preserved with Na2S and LV infarct scar size was smaller in Na2S group as compared to control. Apoptotic signaling, measured by Bcl-2/Bax ratio, was significantly increased in the saline group but was mitigated with Na2S. Survival rate was 2-fold higher in Na2S group compared to saline control ( P < .05). Proteomic analysis and Matrix-Assisted Laser Desorption/Ionization-Time of Flight (TOF)/TOF tandem mass spectrometry identified significant changes in proapoptotic cofilin-2 expression, a specific target of miR-21, between saline- and sodium sulfide -treated mice at 28 days post-MI. Western blot analysis confirmed a significant increase in cofilin-2 after MI, which was suppressed with Na2S treatment. Chronic Na2S treatment also attenuated inflammasome formation and activation leading to reduction of maladaptive signaling. Conclusion: Na2S treatment after MI preserves LV function and improves survival through attenuation of inflammasome-mediated adverse remodeling. We propose H2S donors as promising therapeutic tools for ischemic HFrEF.

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