Non-responsiveness to cardioprotection by ischaemic preconditioning in Ossabaw minipigs with genetic predisposition to, but without the phenotype of the metabolic syndrome
AbstractThe translation of successful preclinical and clinical proof-of-concept studies on cardioprotection to the benefit of patients with reperfused acute myocardial infarction has been difficult so far. This difficulty has been attributed to confounders which patients with myocardial infarction typically have but experimental animals usually not have. The metabolic syndrome is a typical confounder. We hypothesised that there may also be a genuine non-responsiveness to cardioprotection and used Ossabaw minipigs which have the genetic predisposition to develop a diet-induced metabolic syndrome, but before they had develop...
Source: Basic Research in Cardiology - November 11, 2022 Category: Cardiology Source Type: research
Clonal hematopoiesis and cardiovascular disease: deciphering interconnections
AbstractCardiovascular and oncological diseases represent the global major causes of death. For both, a novel and far-reaching risk factor has been identified: clonal hematopoiesis (CH). CH is defined as clonal expansion of peripheral blood cells on the basis of somatic mutations, without overt hematological malignancy. The most commonly affected genes areTET2,DNMT3A,ASXL1 andJAK2. By the age of 70, at least 20 –50% of all individuals carry a CH clone, conveying a striking clinical impact by increasing all-cause mortality by 40%. This is due predominantly to a nearly two-fold increase of cardiovascular risk, but also to ...
Source: Basic Research in Cardiology - November 10, 2022 Category: Cardiology Source Type: research
Retraction Note to: Amphiregulin enhances cardiac fibrosis and aggravates cardiac dysfunction in mice with experimental myocardial infarction partly through activating EGFR ‑dependent pathway
(Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - November 7, 2022 Category: Cardiology Source Type: research
Desmin intermediate filaments and tubulin detyrosination stabilize growing microtubules in the cardiomyocyte
AbstractIn heart failure, an increased abundance of post-translationally detyrosinated microtubules stiffens the cardiomyocyte and impedes its contractile function. Detyrosination promotes interactions between microtubules, desmin intermediate filaments, and the sarcomere to increase cytoskeletal stiffness, yet the mechanism by which this occurs is unknown. We hypothesized that detyrosination may regulate the growth and shrinkage of dynamic microtubules to facilitate interactions with desmin and the sarcomere. Through a combination of biochemical assays and direct observation of growing microtubule plus-ends in adult cardi...
Source: Basic Research in Cardiology - November 3, 2022 Category: Cardiology Source Type: research
Molecular imaging of the brain –heart axis provides insights into cardiac dysfunction after cerebral ischemia
AbstractIschemic stroke imparts elevated risk of heart failure though the underlying mechanisms remain poorly described. We aimed to characterize the influence of cerebral ischemic injury on cardiac function using multimodality molecular imaging to investigate brain and cardiac morphology and tissue inflammation in two mouse models of variable stroke severity. Transient middle cerebral artery occlusion (MCAo) generated extensive stroke damage (56.31 ± 40.39 mm3). Positron emission tomography imaging of inflammation targeting the mitochondrial translocator protein (TSPO) revealed localized neuroinflammation at 7 days ...
Source: Basic Research in Cardiology - October 24, 2022 Category: Cardiology Source Type: research
Osteopontin promotes infarct repair
AbstractUnderstanding how macrophages promote myocardial repair can help create new therapies for infarct repair. We aimed to determine what mechanisms underlie the reparative properties of macrophages. Cytokine arrays revealed that neonatal cardiac macrophages from the injured neonatal heart secreted high amounts of osteopontin (OPN). In vitro, recombinant OPN st imulated cardiac cell outgrowth, cardiomyocyte (CM) cell-cycle re-entry, and CM migration. In addition, OPN induced nuclear translocation of the cytoplasmatic yes-associated protein 1 (YAP1) and upregulated transcriptional factors and cell-cycle genes. Signific...
Source: Basic Research in Cardiology - October 14, 2022 Category: Cardiology Source Type: research
Chronic high-rate pacing induces heart failure with preserved ejection fraction-like phenotype in Ossabaw swine
We examined whether chronic cardiometabolic stress in Ossabaw swine, which possess a genetic propensity for obesity and cardiovascular complications, produces an HFpEF-like phenotype. Swine were fed standard chow (lean;n = 13) or an excess calorie, high-fat, high-fructose diet (obese;n = 16) for ~ 18 weeks with lean (n = 5) and obese (n = 8) swine subjected to right ventricular pacing (180 beats/min for ~ 4 weeks) to induce heart failure (HF). Baseline blood pressure, heart rate, LV end-diastolic volume, and ejection fraction were similar between groups. High-rate pacing increased LV end-diastolic...
Source: Basic Research in Cardiology - October 12, 2022 Category: Cardiology Source Type: research
Remote Ischemic Conditioning: more explanations and more expectations
(Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - October 11, 2022 Category: Cardiology Source Type: research
Cardiomyocyte p38 MAPK α suppresses a heart–adipose tissue–neutrophil crosstalk in heart failure development
AbstractAlthough p38 MAP Kinase α (p38 MAPKα) is generally accepted to play a central role in the cardiac stress response, to date its function in maladaptive cardiac hypertrophy is still not unambiguously defined. To induce a pathological type of cardiac hypertrophy we infused angiotensin II (AngII) for 2 days via osmotic mini pumps in control and tamoxifen-inducible, cardiomyocyte (CM)-specific p38 MAPKα KO mice (iCMp38αKO) and assessed cardiac function by echocardiography, complemented by transcriptomic, histological, and immune cell analysis. AngII treatment after inactivation of p38 MAPKα in CM results in left v...
Source: Basic Research in Cardiology - October 7, 2022 Category: Cardiology Source Type: research
