Myocardial Recovery versus Myocardial Regeneration: Mechanisms and Therapeutic Modulation.

Myocardial recovery is characterized by a return toward normal structure and function of the heart after an injury. Mechanisms of myocardial recovery include restoration and/or adaptation of myocyte structure and function, mitochondrial activity and number, metabolic homeostasis, electrophysiological stability, extracellular matrix remodeling, and myocardial perfusion. Myocardial regeneration is an element of myocardial recovery that involves the generation of new myocardial tissue, a process which is limited in adult humans but may be therapeutically augmented.

Mitochondrial Ca Uniporter-Dependent Energetic Dysfunction Drives Hypertrophy in Heart Failure.

The role of the mitochondrial calcium uniporter (MCU) in energy dysfunction and hypertrophy in heart failure (HF) remains unknown. In angiotensin II (ANGII)-induced hypertrophic cardiac cells we have shown that hypertrophic cells overexpress MCU and present bioenergetic dysfunction. However, by silencing MCU, cell hypertrophy and mitochondrial dysfunction are prevented by blocking mitochondrial calcium overload, increase mitochondrial reactive oxygen species, and activation of nuclear factor kappa B-dependent hypertrophic and proinflammatory signaling.

Future Impact of mRNA Therapy on Cardiovascular Diseases.

The silver lining of the recent pandemic was that it accelerated the emergence of messenger ribonucleic acid (mRNA) therapeutics. The great promise of mRNA therapeutics was highlighted by the speed at which the vaccines were created, tested, and proven to be relatively safe and highly effective. There are a wide variety of mRNA therapeutics now under development, and dozens of these are in clinical trials.

Long term development of diastolic dysfunction and heart failure with preserved left ventricular ejection fraction in heart transplant recipients.

Heart transplant recipients (HTX) have several risk factors for heart failure which can trigger pro-inflammatory and fibrosis factors and set into motion pathophysiologic changes leading to diastolic dysfunction and HFpEF. The objective of the study was to determine if HTX recipients with dyspnea have diastolic dysfunction and HFpEF. Twenty-five HTX were included.

Platelet rich plasma concentration improves biologic mesh incorporation and decreases multinucleated giant cells in a dose dependent fashion.

Platelet rich plasma (PRP) has been shown to improve incorporation and reduce inflammation in ventral hernia repair (VHR) with acellular dermal matrix (ADM). The concentration of platelets in PRP varies in clinical studies and an ideal concentration has yet to be defined. The effects of varied concentrations of PRP on ADM incorporation and inflammatory cell infiltration in a rat model of VHR.

Role of Endothelial and Mesenchymal Cell Transitions in Heart Failure and Recovery Thereafter.

Mechanisms of myocardial recovery are not well elucidated. 3-month-old C57/BL6 mice were treated with Angiotensin-II infusion and N (w)-nitro-L-arginine methyl ester in drinking water to induce HF at 5 weeks. These agents were discontinued, and animals studied with echocardiographic, histological and genetic assessment every 2 weeks until week 19.

Endothelial Dysfunction-related Neurological Bleeds with Continuous Flow-Left Ventricular Assist Devices Measured by Digital Thermal Monitor.

Endothelial dysfunction has been demonstrated in patients with Continuous Flow-Left Ventricular Assist Devices (CF-LVADs) but association with adverse events has not been shown. We used a noninvasive, operator-independent device called VENDYS® to assess vasodilatory function based on digital thermal measurements postrelease of a brachial artery occlusion in ambulatory patients with CF-LVAD (n = 56). Aortic valve opening and pulse perception were also documented before the test.

Small molecule disruption of G protein βγ subunit signaling reprograms human macrophage phenotype and prevents autoimmune myocarditis in rats.

The purpose of this study was to determine whether blocking of G protein βγ (Gβγ) signaling halts heart failure (HF) progression by macrophage phenotype manipulation. Cardiac Gβγ signaling plays a crucial role in HF pathogenesis. Previous data suggested that inhibiting Gβγ signaling reprograms T helper cell 1 (Th1) and Th2 cytokines, suggesting that Gβγ might be a useful drug target for treating HF.

Efficacy of sustained delivery of GC-1 from a Nanofluidic system in a spontaneously obese non-human primate: a case study.

With nearly 40% of U.S. adults obese, and childhood and adolescent rates rising, obesity and associated comorbidities are serious public health concerns with massive societal costs.

Inducible Lung Epithelial Resistance Requires Multisource Reactive Oxygen Species Generation To Protect against Viral Infections.

Viral pneumonias cause profound worldwide morbidity, necessitating novel strategies to prevent and treat these potentially lethal infections. Stimulation of intrinsic lung defenses via inhalation of synergistically acting Toll-like receptor (TLR) agonists protects mice broadly against pneumonia, including otherwise-lethal viral infections, providing a potential opportunity to mitigate infectious threats. As intact lung epithelial TLR signaling is required for the inducible resistance and as these cells are the principal targets of many respiratory viruses, the capacity of lung epithelial cells to be therapeutically manipulated to function as autonomous antiviral effectors was investigated.

Functionally redundant control of cardiac hypertrophic signaling by inositol 1,4,5-trisphosphate receptors.

Calcium plays an integral role to many cellular processes including contraction, energy metabolism, gene expression, and cell death. The inositol 1, 4, 5-trisphosphate receptor (IPR) is a calcium channel expressed in cardiac tissue. There are three IPR isoforms encoded by separate genes.

Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis.

Background And Purpose: Group III pulmonary hypertension (PH) is a highly lethal and widespread lung disorder that is a common complication in idiopathic pulmonary fibrosis (IPF) where it is considered to be the single most significant predictor of mortality. While increased levels of hyaluronan have been observed in IPF patients, hyaluronan-mediated vascular remodelling and the hyaluronan-mediated mechanisms promoting PH associated with IPF are not fully understood.

Experimental Approach: Explanted lung tissue from patients with IPF with and without a diagnosis of PH was used to identify increased levels of hyaluronan.

Epithelial to Mesenchymal Transition (EMT) and Endothelial to Mesenchymal Transition (EndMT): Role and Implications in Kidney Fibrosis.

Tubulointerstitial injury is one of the hallmarks of renal disease. In particular, interstitial fibrosis has a prominent role in the development and progression of kidney injury. Collagen-producing fibroblasts are responsible for the ECM deposition.

Rapamycin nanoparticles localize in diseased lung vasculature and prevent pulmonary arterial hypertension.

Vascular remodeling resulting from pulmonary arterial hypertension (PAH) leads to endothelial fenestrations. This feature can be exploited by nanoparticles (NP), allowing them to extravasate from circulation and accumulate in remodeled pulmonary vessels. Hyperactivation of the mTOR pathway in PAH drives pulmonary arterial smooth muscle cell proliferation.

AIBP Limits Angiogenesis Through γ-Secretase-Mediated Upregulation of Notch Signaling.

Rationale: Angiogenesis improves perfusion to the ischemic tissue after acute vascular obstruction. Angiogenesis in pathophysiological settings reactivates signaling pathways involved in developmental angiogenesis. We showed previously that AIBP (apolipoprotein A-I [apoA-I]-binding protein)-regulated cholesterol efflux in endothelial cells controls zebra fish embryonic angiogenesis.

Pulmonary Hypertension Associated with Idiopathic Pulmonary Fibrosis: Current and Future Perspectives.

Pulmonary hypertension (PH) is commonly present in patients with chronic lung diseases such as Chronic Obstructive Pulmonary Disease (COPD) or Idiopathic Pulmonary Fibrosis (IPF) where it is classified as Group III PH by the World Health Organization (WHO). PH has been identified to be present in as much as 40% of patients with COPD or IPF and it is considered as one of the principal predictors of mortality in patients with COPD or IPF. However, despite the prevalence and fatal consequences of PH in the setting of chronic lung diseases, there are limited therapies available for patients with Group III PH, with lung transplantation remaining as the most viable option.

MicroRNA-126 overexpression rescues diabetes-induced impairment in efferocytosis of apoptotic cardiomyocytes.

Efferocytosis, a process of clearance of apoptotic cells by phagocytes, is essential for successful resolution of inflammation and maintenance of tissue homeostasis. Diabetes compromises the function of macrophages leading to adverse inflammatory response during wound healing, myocardial injury, atherosclerosis and autoimmune disorders. However, the effect of diabetes on macrophage-mediated efferocytosis of apoptotic cardiomyocytes (ACM) and the molecular mechanisms involved are not understood so far.

Macrophage bone morphogenic protein receptor 2 depletion in idiopathic pulmonary fibrosis and Group III pulmonary hypertension.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. The development of pulmonary hypertension (PH) is considered the single most significant predictor of mortality in patients with chronic lung diseases. The processes that govern the progression and development of fibroproliferative and vascular lesions in IPF are not fully understood.

MicroRNA-9 inhibits hyperglycemia-induced pyroptosis in human ventricular cardiomyocytes by targeting ELAVL1.

Diabetic cardiomyopathy is a common complication in patients with diabetes and is associated with underlying chronic inflammation and cardiac cell death, subsequently leading to heart failure (HF). ELAV-like protein 1 (ELAVL1) plays a critical role in the progression of inflammation and HF. However the role of ELAVL-1 in inflammation induced cardiac cell death (pyroptosis) under hyperglycemic condition remains elusive.