Adipocyte-derived small extracellular vesicles exacerbate diabetic ischemic heart injury by promoting oxidative stress and mitochondrial-mediated cardiomyocyte apoptosis.

Background: Diabetes increases ischemic heart injury via incompletely understood mechanisms. We recently reported that diabetic adipocytes-derived small extracellular vesicles (sEV) exacerbate myocardial reperfusion (MI/R) injury by promoting cardiomyocyte apoptosis. Combining in vitro mechanistic investigation and in vivo proof-concept demonstration, we determined the underlying molecular mechanism responsible for diabetic sEV-induced cardiomyocyte apoptosis after MI/R.

COVID-19 and cardiovascular complications: updates of emergency medicine.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV-2 variants, has become a global pandemic resulting in significant morbidity and mortality. Severe cases of COVID-19 are characterized by hypoxemia, hyper-inflammation, cytokine storm in lung. Clinical studies have reported an association between COVID-19 and cardiovascular disease (CVD).

Dysfunctional APPL1-Mediated Epigenetic Regulation in Diabetic Vascular Injury.

Background: APN (adiponectin) and APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) are potent vasculoprotective molecules, and their deficiency (eg, hypoadiponectinemia) contributes to diabetic vascular complications. However, the molecular mechanisms that govern their vasculoprotective genes as well as their alteration by diabetes remain unknown.

Methods: Diabetic medium-cultured rat aortic endothelial cells, mouse aortic endothelial cells from high-fat-diet animals, and diabetic human aortic endothelial cells were used for molecular/cellular investigations.

Hypoadiponectinemia-induced upregulation of microRNA449b downregulating Nrf-1 aggravates cardiac ischemia-reperfusion injury in diabetic mice.

Diabetes enhances myocardial ischemic/reperfusion (MI/R) injury via an incompletely understood mechanism. Adiponectin (APN) is a cardioprotective adipokine suppressed by diabetes. However, how hypoadiponectinemia exacerbates cardiac injury remains incompletely understood.

Nitrative Modification of Caveolin-3: A Novel Mechanism of Cardiac Insulin Resistance and a Potential Therapeutic Target Against Ischemic Heart Failure in Prediabetic Animals.

Background: Myocardial insulin resistance is a hallmark of diabetic cardiac injury. However, the underlying molecular mechanisms remain unclear. Recent studies demonstrate that the diabetic heart is resistant to other cardioprotective interventions, including adiponectin and preconditioning.

Targeting Adiponectin Receptor 1 Phosphorylation Against Ischemic Heart Failure.

Background: Despite significantly reduced acute myocardial infarction (MI) mortality in recent years, ischemic heart failure continues to escalate. Therapeutic interventions effectively reversing pathological remodeling are an urgent unmet medical need. We recently demonstrated that AdipoR1 (APN [adiponectin] receptor 1) phosphorylation by GRK2 (G-protein-coupled receptor kinase 2) contributes to maladaptive remodeling in the ischemic heart.

C1q/TNF-Related Protein 3 Prevents Diabetic Retinopathy via AMPK-Dependent Stabilization of Blood-Retinal Barrier Tight Junctions.

The impairment of the inner blood-retinal barrier (iBRB) increases the pathological development of diabetic retinopathy (DR), a severe complication in diabetic patients. Identifying approaches to preserving iBRB integrity and function is a significant challenge in DR. C1q/tumor necrosis factor-related protein-3 (CTRP3) is a newly discovered adipokine and a vital biomarker, predicting DR severity.

Ischemic Heart-Derived Small Extracellular Vesicles Impair Adipocyte Function.

Background: Patients with acute myocardial infarction suffer systemic metabolic dysfunction via incompletely understood mechanisms. Adipocytes play critical role in metabolic homeostasis. The impact of acute myocardial infarction upon adipocyte function is unclear.

C1q Complement/Tumor Necrosis Factor-Associated Proteins in Cardiovascular Disease and COVID-19.

With continually improving treatment strategies and patient care, the overall mortality of cardiovascular disease (CVD) has been significantly reduced. However, this success is a double-edged sword, as many patients who survive cardiovascular complications will progress towards a chronic disorder over time. A family of adiponectin paralogs designated as C1q complement/tumor necrosis factor (TNF)-associated proteins (CTRPs) has been found to play a role in the development of CVD.

Identification of a CTRP9 C-Terminal polypeptide capable of enhancing bone-derived mesenchymal stem cell cardioprotection through promoting angiogenic exosome production.

Background: Mesenchymal stem cell therapy improves ischemic heart failure via incompletely understood mechanisms. C1q-TNFα related protein-9 (CTRP9) is a novel anti-oxidative cardiokine capable of improving the local microenvironment and cell survival by its c-terminal active globular domain (gCTRP9). The current study attempted to: 1) identify active gCTRP9 c-terminal polypeptides with stem cell protective function; 2) determine whether a lead polypeptide may enable/enhance cortical bone-derived mesenchymal stem cell (CBSC) cardioprotection against post-myocardial infarction (post-MI) remodeling; and 3) define the responsible underlying cellular/molecular mechanisms.

Nicotine induces cardiac toxicity through blocking mitophagic clearance in young adult rat.

Since an outbreak of vaping-related deaths in the US has been reported as a public health crisis, the cardiovascular safety of nicotine nowadays receives increasing attention due to use of tobacco cigarette alternatives, such as electronic cigarettes. However, whether and how nicotine contributes to cardiac detrimental effects are in great controversy, especially less understood in young adult population. We report that chronic nicotine exposure, a major component of Electronic cigarettes, resulted in directly inhibited cardiomyocytes viability, increased cardiac fibrosis, and markedly suppressed cardiac function compared with sham.

Adiponectin inhibits cardiac arrest/cardiopulmonary resuscitation‑induced apoptosis in brain by increasing autophagy involved in AdipoR1‑AMPK signaling.

Emerging evidence suggests that both apoptosis and autophagy contribute to global cerebral ischemia‑reperfusion (GCIR)‑induced neuronal death, which results from cardiac arrest (CA). However, the mechanism of how GCIR may affect the balance between apoptosis and autophagy resulting from CA remains to be elucidated. Additionally, the role of adiponectin (APN) in reversing the apoptosis and autophagy induced by GCIR following cardiac arrest‑cardiopulmonary resuscitation (CA‑CPR) is unclear.

C1q/TNF-related protein 5 contributes to diabetic vascular endothelium dysfunction through promoting Nox-1 signaling.

Objective: Dysregulated adipokine profiles contribute to the pathogenesis of diabetic cardiovascular complications. Endothelial cell (EC) dysfunction, a common pathological alteration in cardiovascular disorders, is exaggerated in diabetes. However, it is unclear whether and how dysregulated adipokines may contribute to diabetic EC dysfunction.

Small Extracellular Microvesicles Mediated Pathological Communications Between Dysfunctional Adipocytes and Cardiomyocytes as a Novel Mechanism Exacerbating Ischemia/Reperfusion Injury in Diabetic Mice.

Background: Diabetes mellitus exacerbates myocardial ischemia/reperfusion (MI/R) injury by incompletely understood mechanisms. Adipocyte dysfunction contributes to remote organ injury. However, the molecular mechanisms linking dysfunctional adipocytes to increased MI/R injury remain unidentified.

Sevoflurane Pre-conditioning Ameliorates Diabetic Myocardial Ischemia/Reperfusion Injury Via Differential Regulation of p38 and ERK.

Diabetes mellitus (DM) significantly increases myocardial ischemia/reperfusion (MI/R) injury. During DM, cardioprotection induced by conventional pre-conditioning (PreCon) is decreased due to impaired AMP-activated protein kinase (AMPK) signaling. The current study investigated whether PreCon with inhaled anesthetic sevoflurane (SF-PreCon) remains cardioprotective during DM, and identified the involved mechanisms.

miRNA-Mediated Suppression of a Cardioprotective Cardiokine as a Novel Mechanism Exacerbating Post-MI Remodeling by Sleep Breathing Disorders.

Rationale: Obstructive sleep apnea-hypopnea syndrome, a sleep breathing disorder in which chronic intermittent hypoxia (CIH) is the primary pathology, is associated with multiple cardiovascular diseases. However, whether and how CIH may affect cardiac remodeling following myocardial infarction (MI) remains unknown.

Objective: To determine whether CIH exposure at different periods of MI may exacerbate post-MI heart failure and to identify the mechanisms underlying CIH-exacerbated post-MI remodeling.

Withaferin A Prevents Myocardial Ischemia/Reperfusion Injury by Upregulating AMP-Activated Protein Kinase-Dependent B-Cell Lymphoma2 Signaling.

Background: Withaferin A (WFA), an anticancer constituent of the plant Withania somnifera, inhibits tumor growth in association with apoptosis induction. However, the potential role of WFA in the cardiovascular system is little-studied and controversial.

Methods and results: Two different doses of WFA were tested to determine their cardioprotective effects in myocardial ischemia/reperfusion (MI/R) injury through evaluation of cardiofunction in wild-type and AMP-activated protein kinase domain negative (AMPK-DN) gentransgenic mice.

Withaferin A inhibits apoptosis via activated Akt-mediated inhibition of oxidative stress.

Withaferin A (WFA), a withanolide derived from medicinal plant Withania somnifera, possesses anti-tumorigenic and immunomodulatory activities against various cancer cells. However, the role of WFA in myocardial ischemia reperfusion (MI/R) injury remains unclear. In the present study, we determined whether WFA may regulate cardiac ischemia reperfusion injury and elucidate the underlying mechanisms.

Adiponectin at Physiologically Relevant Concentrations Enhances the Vasorelaxative Effect of Acetylcholine via Cav-1/AdipoR-1 Signaling.

Clinical studies have identified hypoadiponectinemia as an independent hypertension risk factor. It is known that adiponectin (APN) can directly cause vasodilation, but the doses required exceed physiologic levels several fold. In the current study, we determine the effect of physiologically relevant APN concentrations upon vascular tone, and investigate the mechanism(s) responsible.

High glucose/High Lipids impair vascular adiponectin function via inhibition of caveolin-1/AdipoR1 signalsome formation.

Reduced levels of adiponectin (APN) contribute to cardiovascular injury in the diabetic population. Recent studies demonstrate elevated circulating APN levels are associated with endothelial dysfunction during pre-diabetes, suggesting the development of APN resistance. However, mechanisms leading to, and the role of, vascular APN resistance in endothelial dysfunction remain unidentified.

C1q-TNF-related protein-9, a novel cardioprotetcive cardiokine, requires proteolytic cleavage to generate a biologically active globular domain isoform.

Prevalence and severity of postmyocardial infarction heart failure continually escalate in type 2 diabetes via incompletely understood mechanisms. The discovery of the cardiac secretomes, collectively known as "cardiokines", has significantly enhanced appreciation of the local microenvironment's influence on disease development. Recent studies demonstrated that C1q-TNF-related protein-9 (CTRP9), a newly discovered adiponectin (APN) paralog, is highly expressed in the heart.

The development of the emergency medicine milestones.

The Accreditation Council for Graduate Medical Education (ACGME) has outlined its "Next Accreditation System" (NAS) that will focus on resident and residency outcome measurements. Emergency medicine (EM) is one of seven specialties that will implement the NAS beginning July 2013. All other specialties will follow in July 2014.

Lymphotoxin-α is a novel adiponectin expression suppressor following myocardial ischemia/reperfusion.

Recent clinical observations demonstrate adiponectin (APN), an adipocytokine with potent cardioprotective actions, is significantly reduced following myocardial ischemia/reperfusion (MI/R). However, mechanisms responsible for MI/R-induced hypoadiponectinemia remain incompletely understood. Adult male mice were subjected to 30-min MI followed by varying reperfusion periods.

C1q/TNF-related proteins, a family of novel adipokines, induce vascular relaxation through the adiponectin receptor-1/AMPK/eNOS/nitric oxide signaling pathway.

Objective: Reduced plasma adiponectin (APN) in diabetic patients is associated with endothelial dysfunction. However, APN knockout animals manifest modest systemic dysfunction unless metabolically challenged. The protein family CTRPs (C1q/TNF-related proteins) has recently been identified as APN paralogs and some CTRP members share APN's metabolic regulatory function.