Regulation of STAT3 and its role in cardioprotection by conditioning: focus on non-genomic roles targeting mitochondrial function
AbstractIschemia –reperfusion injury (IRI) is one of the biggest challenges for cardiovascular researchers given the huge death toll caused by myocardial ischemic disease. Cardioprotective conditioning strategies, namely pre- and post-conditioning maneuvers, represent the most important strategies for stimulating pro-survival pathways essential to preserve cardiac health. Conditioning maneuvers have proved to be fundamental for the knowledge of the molecular basis of both IRI and cardioprotection. Among this evidence, the importance of signal transducer and activator of transcription 3 (STAT3) emerged. STAT3 is not only ...
Source: Basic Research in Cardiology - October 12, 2021 Category: Cardiology Source Type: research

Resolving the intertwining of inflammation and fibrosis in human heart failure at single-cell level
AbstractInflammation and fibrosis are intertwined mechanisms fundamentally involved in heart failure. Detailed deciphering gene expression perturbations and cell –cell interactions of leukocytes and non-myocytes is required to understand cell-type-specific pathology in the failing human myocardium. To this end, we performed single-cell RNA sequencing and single T cell receptor sequencing of 200,615 cells in both human dilated cardiomyopathy (DCM) and ische mic cardiomyopathy (ICM) hearts. We sampled both lesion and mild-lesion tissues from each heart to sequentially capture cellular and molecular alterations to different...
Source: Basic Research in Cardiology - October 3, 2021 Category: Cardiology Source Type: research

The zinc transporter ZIP7 (Slc39a7) controls myocardial reperfusion injury by regulating mitophagy
AbstractWhereas elimination of damaged mitochondria by mitophagy is proposed to be cardioprotective, the regulation of mitophagy at reperfusion and the underlying mechanism remain elusive. Since mitochondrial Zn2+ may control mitophagy by regulating mitochondrial membrane potential (MMP), we hypothesized that the zinc transporter ZIP7 that controls Zn2+ levels within mitochondria would contribute to reperfusion injury by regulating mitophagy. Mouse hearts were subjected to ischemia/reperfusion in vivo. Mitophagy was evaluated by detecting mitoLC3II, mito-Keima, and mitoQC. ROS were measured with DHE and mitoB. Infarct size...
Source: Basic Research in Cardiology - September 28, 2021 Category: Cardiology Source Type: research

The miR-182/Myadm axis regulates hypoxia-induced pulmonary hypertension by balancing the BMP- and TGF- β-signalling pathways in an SMC/EC-crosstalk-associated manner
AbstractWe recently identified oncologic miR-182 as a new regulator of pulmonary artery hypertension (PAH) that targets myeloid-associated differentiation marker (Myadm), which is expressed in bone marrow stem cells and multipotent progenitors. Both miR-182 and Myadm are expressed in the cardiopulmonary system and correlated with the balance between the bone morphogenetic protein (BMP) and the transforming growth factor (TGF)- β signalling pathways, which are disturbed in PAH. We hypothesize that miR-182/Myadm are involved in BMP-TGF-β-signalling way in PAH. Hypoxia triggered pathological progression in cardiopulmonary P...
Source: Basic Research in Cardiology - September 21, 2021 Category: Cardiology Source Type: research

IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria: guidelines of the EU-CARDIOPROTECTION COST Action
AbstractAcute myocardial infarction (AMI) and the heart failure (HF) which may follow are among the leading causes of death and disability worldwide. As such, new therapeutic interventions are still needed to protect the heart against acute ischemia/reperfusion injury to reduce myocardial infarct size and prevent the onset of HF in patients presenting with AMI. However, the clinical translation of cardioprotective interventions that have proven to be beneficial in preclinical animal studies, has been challenging. One likely major reason for this failure to translate cardioprotection into patient benefit is the lack of rigo...
Source: Basic Research in Cardiology - September 13, 2021 Category: Cardiology Source Type: research

Impaired pulmonary vasomotor control in exercising swine with multiple comorbidities
In conclusion, common comorbidities directly alter pulmonary vascular control, by enhanced PDE5 and endothelin-mediated vasoconstrictor influences, well before overt left ventricular backward failure or pulmonary hypertension develop. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - September 12, 2021 Category: Cardiology Source Type: research

Reduced nitric oxide bioavailability impairs myocardial oxygen balance during exercise in swine with multiple risk factors
In conclusion, five months of combined exposure to DM + HFD + CKD produces coronary endothelial dysfunction due to impaired NO bioavailability, resulting in impaired myocardial perfusion at rest and during exercise. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - August 26, 2021 Category: Cardiology Source Type: research

Mitochondrial nucleoid in cardiac homeostasis: bidirectional signaling of mitochondria and nucleus in cardiac diseases
AbstractMetabolic function and energy production in eukaryotic cells are regulated by mitochondria, which have been recognized as the intracellular ‘powerhouses’ of eukaryotic cells for their regulation of cellular homeostasis. Mitochondrial function is important not only in normal developmental and physiological processes, but also in a variety of human pathologies, including cardiac diseases. An emerging topic in the field of cardiovascul ar medicine is the implication of mitochondrial nucleoid for metabolic reprogramming. This review describes the linear/3D architecture of the mitochondrial nucleoid (e.g., highly or...
Source: Basic Research in Cardiology - August 14, 2021 Category: Cardiology Source Type: research