Left Ventricular Systolic Dysfunction in NBCe1-B/C-Knockout Mice.

Congenital proximal renal tubular acidosis (pRTA) is a rare systemic disease caused by mutations in the gene that encodes the electrogenic sodium bicarbonate cotransporter, NBCe1. The major NBCe1 protein variants are designated NBCe1-A, NBCe1-B, and NBCe1-C. NBCe1-A expression is kidney-specific, NBCe1-B is broadly expressed and is the only NBCe1 variant expressed in the heart, and NBCe1-C is a splice variant of NBCe1-B that is expressed in the brain.

Porcine Model of Hypertrophy-Independent Left Ventricular Stiffening via Repetitive Pressure Overload.

Diastolic dysfunction arising from alterations in myocardial structure and/or function is a central component of several cardiovascular disorders, including heart failure with preserved ejection fraction (HFpEF). Basic research aimed at understanding underlying mechanisms contributing to the development of diastolic dysfunction has generally centered upon models of left ventricular (LV) hypertrophy arising from persistent and severe elevations in myocardial afterload (e.g.

Survivin regulates intracellular stiffness and extracellular matrix production in vascular smooth muscle cells.

Vascular dysfunction is a common cause of cardiovascular diseases characterized by the narrowing and stiffening of arteries, such as atherosclerosis, restenosis, and hypertension. Arterial narrowing results from the aberrant proliferation of vascular smooth muscle cells (VSMCs) and their increased synthesis and deposition of extracellular matrix (ECM) proteins. These, in turn, are modulated by arterial stiffness, but the mechanism for this is not fully understood.

Galectin-3 Is Associated with Cardiac Fibrosis and an Increased Risk of Sudden Death.

Background: Myocardial fibrosis is a common postmortem finding among individuals with Sudden Cardiac Death (SCD). Numerous in vivo and in vitro studies have shown that increased galectin-3 (gal3) expression into the myocardium is associated with higher incidence of fibrosis. Although elevated gal3 expression is linked with myocardial fibrosis, its role in predicting the risk of SCD is unknown.

Preclinical evaluation of triiodothyronine nanoparticles as a novel therapeutic intervention for resuscitation from cardiac arrest.

Background: Given emerging evidence of rapid non-genomic cytoprotective effects of triiodothyronine (T3), we evaluated the resuscitative efficacy of two nanoparticle formulations of T3 (T3np) designed to prolong cell membrane receptor-mediated signaling.

Methods: Swine (n = 40) were randomized to intravenous vehicle (empty np), EPI (0.015 mg/kg), T3np (0.

Widespread intracoronary allogeneic cardiosphere-derived cell therapy with and without cyclosporine in reperfused myocardial infarction.

Allogeneic cardiosphere-derived cell (CDC) therapy has been demonstrated to improve myocardial function when administered to reperfused myocardial infarcts. We previously pretreated animals with low-dose cyclosporine immunosuppression to limit allogeneic CDC rejection, but whether it is necessary and, if so, can be initiated at the time of reperfusion remains uncertain. Closed-chest swine ( = 29 animals) were subjected to a 90-min left anterior descending (LAD) coronary artery occlusion.

Correction: Karakus et al. Development of Triiodothyronine Polymeric Nanoparticles for Targeted Delivery in the Cardioprotection against Ischemic Insult. 2021, , 1713.

In the published manuscript [...

Development of Triiodothyronine Polymeric Nanoparticles for Targeted Delivery in the Cardioprotection against Ischemic Insult.

Ischemic heart disease is the main cause of death globally. Cardioprotection is the process whereby mechanisms that reduce myocardial damage, and activate protective factors, contribute to the preservation of the heart. Targeting these processes could be a new strategy in the treatment of post-ischemic heart failure (HF).

Paper-Based Robotics with Stackable Pneumatic Actuators.

This work presents a unique approach to the design, fabrication, and characterization of paper-based origami robotic systems consisting of stackable pneumatic actuators. These paper-based actuators (PBAs) use materials with high elastic modulus-to-mass ratios, accordion-like structures, and direct coupling with pneumatic pressure for extension and bending. The study contributes to the scientific and engineering understanding of foldable components under applied pneumatic pressure by constructing stretchable and flexible structures with intrinsically nonstretchable materials.

Neutrophils aid cellular therapeutics by enhancing glycoengineered stem cell recruitment and retention at sites of inflammation.

The efficacy of cell-based therapies relies on targeted payload delivery and enhanced cell retention. In vitro and in vivo studies suggest that the glycoengineering of mesenchymal and cardiosphere-derived cells (CDCs) may enhance such recruitment at sites of injury. We evaluated the role of blood cells in amplifying this recruitment.

Quantitative proteomic and phosphoproteomic profiling of ischemic myocardial stunning in swine.

Despite decades of research on the pathophysiology of myocardial stunning, protein changes and/or phosphorylation status underlying alterations in cardiac function/structure remain inadequately understood. Here, we utilized comprehensive and quantitative proteomic and phosphoproteomic approaches to explore molecular mechanisms of myocardial stunning in swine. The closed-chest swine ( = 5 pigs) were subjected to a 10-min left anterior descending coronary artery (LAD) occlusion producing regional myocardial stunning.

Transmural variation in microvascular remodeling following percutaneous revascularization of a chronic coronary stenosis in swine.

Remodeling of the coronary microcirculation is known to occur distal to a chronic coronary stenosis, but the reversibility of these changes and their functional significance on maximum myocardial perfusion before and after revascularization is unknown. Accordingly, swine instrumented with a chronic silastic stenosis on the left anterior descending coronary artery to produce hibernating myocardium underwent percutaneous coronary intervention (PCI; = 8) and were compared with animals with a persistent stenosis ( = 8), as well as sham controls ( = 6). Stenotic animals demonstrated an increased subendocardial arteriolar wall thickness-to-lumen ratio (37.

Adaptive Reductions in Left Ventricular Diastolic Compliance Protect the Heart From Stretch-Induced Stunning.

Swine subjected to 2 weeks of repetitive pressure overload (RPO) exhibited significant myocyte loss, but left ventricular (LV) systolic function was preserved, and chamber dilatation did not occur. Instead, myocardial remodeling characterized by myocyte hypertrophy and interstitial fibrosis led to a marked reduction in LV diastolic compliance, which protected the heart from stretch-induced myocyte injury and preserved LV ejection fraction without anatomic LV hypertrophy. These results support a novel paradigm that links cardiac adaptations to RPO with the pathogenesis of reduced LV diastolic compliance and may explain how LV stiffening can occur in the absence of sustained hypertension or anatomic hypertrophy.

Nonocclusive multivessel intracoronary infusion of allogeneic cardiosphere-derived cells early after reperfusion prevents remote zone myocyte loss and improves global left ventricular function in swine with myocardial infarction.

Intracoronary cardiosphere-derived cells (icCDCs) infused into the infarct-related artery reduce scar volume but do not improve left ventricular (LV) ejection fraction (LVEF). We tested the hypothesis that this reflects the inability of regional delivery to prevent myocyte death or promote myocyte proliferation in viable myocardium remote from the infarct. Swine ( = 23) pretreated with oral cyclosporine (200 mg/day) underwent a 1-h left anterior descending coronary artery (LAD) occlusion, which reduced LVEF from 61.

Selectins and Immune Cells in Acute Myocardial Infarction and Post-infarction Ventricular Remodeling: Pathophysiology and Novel Treatments.

The glycosciences aim to understand the impact of extracellular and intracellular carbohydrate structures on biological function. These glycans primarily fall into three major groups: lipid-linked carbohydrates that are referred to as glycosphingolipids or simply glycolipids; relatively short carbohydrate chains that are often O- or N-linked to proteins yielding common glycoproteins; and extended linear polymeric carbohydrate structures that are referred to as glycosaminoglycans (GAGs). Whereas, the impact of such carbohydrate structures has been extensively examined in cancer biology, their role in acute and chronic heart disease is less studied.

Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction.

Background: After myocardial infarction (MI), inflammatory cells infiltrate the infarcted heart in response to secreted stimuli. Monocytes are recruited to the infarct via CCR2 chemokine receptors along a CCL2 concentration gradient. While infiltration of injured tissue with monocytes is an important component of the reparatory response, excessive or prolonged inflammation can adversely affect left ventricular remodeling and worsen clinical outcomes.

Effect of Intracoronary Metformin on Myocardial Infarct Size in Swine.

Rationale: Metformin has been demonstrated to decrease infarct size (IS) and prevent postinfarction left ventricular (LV) remodeling in rodents when given intravenously at the time of reperfusion. It remains unclear whether similar cardioprotection can be achieved in a large animal model.

Objective: The objective of this study was to determine whether intravascular infusion of metformin at the time of reperfusion reduces myocardial IS in a porcine model of acute myocardial infarction.

Troponin Release and Reversible Left Ventricular Dysfunction After Transient Pressure Overload.

Background: The authors previously demonstrated that brief ischemia elicits cardiac troponin I (cTnI) release and myocyte apoptosis in the absence of necrosis. It remains uncertain whether other pathophysiological stresses can produce apoptosis and transient cTnI release without ischemia.

Objectives: This study sought to determine whether a transient increase in left ventricular (LV) preload elicits cTnI release in the absence of ischemia.

Brief Myocardial Ischemia Produces Cardiac Troponin I Release and Focal Myocyte Apoptosis in the Absence of Pathological Infarction in Swine.

In a porcine model of brief ischemia leading to reversible stunning in the absence of tissue necrosis, we demonstrated delayed release of cTnI that exceeded the 99 percentile for normals 60-minutes after reperfusion and rose to readily detectable levels 24-hours later. While tissue analysis at 60-minutes showed no evidence of infarction, TUNEL staining demonstrated isolated myocytes undergoing apoptosis, which was absent after 24-hours. These results demonstrate that cTnI elevations occur after ischemia of a duration that is insufficient to produce myocyte necrosis and reflect myocyte injury associated with delayed apoptosis in the absence of pathological evidence of infarction.

Insufficient sleep is associated with impaired nitric oxide-mediated endothelium-dependent vasodilation.

Background And Aims: Habitual short nightly sleep duration is associated with increased atherosclerotic cardiovascular disease risk and morbidity. Vascular endothelial dysfunction represents an important mechanism that may underlie this heightened cardiovascular risk. Impaired endothelium-dependent vasodilation, particularly NO-mediated vasodilation, contributes to the development and progression of atherosclerotic vascular disease and acute vascular events.

Myocardial and Serum Galectin-3 Expression Dynamics Marks Post-Myocardial Infarction Cardiac Remodelling.

Background: Acute myocardial infarction (MI) causes significant changes in cardiac morphology and function. Galectin-3 is a novel and potentially therapeutically important mediator of cardiac remodelling. Myocardial and serum galectin-3 expression dynamics in response to the early cardiovascular outcomes after acute MI are not fully elucidated.