Comprehensive viewpoints on heart rate variability at high altitude.

OBJECTIVES: Hypoxia is a physiological state characterized by reduced oxygen levels in organs and tissues. It is a common clinicopathological process and a major cause of health problems in highland areas.  Heart rate variability (HRV) is a measure of the balance in autonomic innervation to the heart. It provides valuable information on the regulation of the cardiovascular system by neurohumoral factors, and changes in HRV reflect the complex interactions between multiple systems. In this review, we provide a comprehensive overview of the relationship between high-altitude hypoxia and HRV. We summarize the different mechanisms of diseases caused by hypoxia and explore the changes in HRV across various systems. Additionally, we discuss relevant pharmaceutical interventions. Overall, this review aims to provide research ideas and assistance for in-depth studies on HRV. By understanding the intricate relationship between high-altitude hypoxia and HRV, we can gain insights into the underlying mechanisms and potential therapeutic approaches to mitigate the effects of hypoxia on cardiovascular and other systems. METHODS: The relevant literature was collected systematically from scientific database, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Baidu Scholar, as well as other literature sources, such as classic books of hypoxia. RESULTS: There is a close relationship between heart rate variability and high-altitude hypoxia. Heart rate variability is an indicator that evaluates the impact of hypoxia on the cardiovascular system and other related systems. By improving the observation of HRV, we can estimate the progress of cardiovascular diseases and predict the impact on other systems related to cardiovascular health. At the same time, changes in heart rate variability can be used to observe the efficacy of preventive drugs for altitude related diseases. CONCLUSIONS: HRV can be used to assess autonomic nervous function under various systemic conditions, and can be used to predict and monitor diseases caused by hypoxia at high altitude. Investigating the correlation between high altitude hypoxia and heart rate variability can help make HRV more rapid, accurate, and effective for the diagnosis of plateau-related diseases.

Inhibition of GPR35 Preserves Mitochondrial Function After Myocardial Infarction by Targeting Calpain 1/2.

Ischemia and anoxia-induced mitochondrial impairment may be a key factor leading to heart injury during myocardial infarction (MI). Calpain 1 and 2 are involved in the MI-induced mitochondria injury. G protein-coupled receptor 35 (GPR35) could be triggered by hypoxia. Whether or not GPR35 regulates calpain 1/2 in the pathogenesis of MI is still unclear. In this study, we determined that MI increases GPR35 expression in myocardial tissue. Suppression of GPR35 protects heart from MI injury in mice through reduction of reactive oxygen species activity and mitochondria-dependent apoptosis. Further studies show that GPR35 regulates calpain 1/2. Suppression of GPR35 reduces the expression and activity of calpain 1/2, and alleviates calpain 1/2-associated mitochondrial injury to preserve cardiac function. Based on these data, we conclude that a functional inhibition of GPR35 downregulates calpain 1/2 and contributes to maintenance of cardiac function under pathologic conditions with mitochondrial disorder. In conclusion, our study showed that the identified regulation by GPR35 of calpain 1/2 has important implications for the pathogenesis of MI. Targeting the action of GPR35 and calpain 1/2 in mitochondria presents a potential therapeutic intervention for MI.

[Study of the Role and Mechanism of Asprosin/Spartin Pathway in Cardiac Microvascular Endothelial Injury Induced by Diabete Mellitus].

OBJECTIVE: To detect the effects and mechanism of asprosin (Asp) and spartin on the injury of mice cardiac microvascular endothelial cells (CMECs) induced by high glucose. METHODS: The cultured CMECs were divided into 2 groups, one group is normal group (5.5 mmol/L glucose in the medium) and another is HG group (30 mmol/L glucose in the medium). Real-time PCR (qRT-PCR) and Western blot were respectively used to detect the mRNA level of spastic paraplegia 20 (SPG20) and protein expression of spartin in CMECs. Upregulation or downregulation of the expression of spartin was achieved via transfection with adenovirus (Ad) or small interfering RNA (siRNA) respectively. CMECs with downregulation of spartin expression were firstly treated with anti-oxidant N-acetylcysteine (NAC) or Asp respectively for 48 h, and then were interfered with 30 mmol/L glucose for 24 h afterward. The apoptosis of cell was detected by flow cytometry. Nitric oxide (NO) production was detected by NO probe and ELISA kit. The intracellular reactive oxygen species (ROS) levels were tested by DHE staining and ELISA kit. Type 2 diabetic model mice were established and then divided into T2DM group and T2DM+Asp group. After the model mice were established successfully (random blood glucose was more than 16.7 mmol/L), Asp (1 µg/g) was intraperitoneally injected once a day. After 2 weeks, mice echocardiography was performed to test cardiac diastolic function. The integrity of the microvascular endothelium was observed by scanning electron microscopy. RESULTS: Compared with the normal group, the mRNA level of SPG20 and protein expression of spartin in mice CMECs of HG group were significantly reduced (P < 0.05). Under the condition of high glucose, Ad transfection induced significant decrease of the intracellular ROS level and the apoptosis level of the CMECs (P < 0.05), while NO increased after Ad transfection. In contrast, siRNA intervention resulted in opposite effect. In addition, the antioxidant NAC partly reversed the above changes caused by downregulating spartin. Asp upregulated the level of SPG20 mRNA and spartin protein expression in CMECs, reduced ROS production, reduced apoptosis and increased NO production. However, intervention effects of Asp, such as decreasing of ROS production, inhibiting apoptosis of CMECs and increasing of NO production, were partly reversed in spartin downregulated cells. In vivo, we found that Asp can improve cardiac function and increase the integrity and smoothness of cardiac microvascular endothelium in type 2 diabetic mice. CONCLUSION: Asp can inhibit oxidative stress in mice CMECs through upregulating spartin signaling pathway, thereby alleviating the damage of microvascular endothelium in diabetic heart.

Activation of transient receptor potential vanilloid 1 accelerates re-endothelialization and inhibits neointimal formation after vascular injury.

OBJECTIVE: Transient receptor potential vanilloid 1 (TRPV1) is an important regulator of endothelial function, but the effects of TRPV1 on endothelial recovery and neointimal formation after vascular injury remain elusive. We tested the effects of activating TRPV1 using capsaicin on re-endothelialization and neointimal formation after wire-induced injury of the carotid artery in mice. METHODS: The human umbilical vein endothelial cells (HUVECs) were treated with the TRPV1 agonist capsaicin, its antagonist capsazepine, intracellular calcium chelator BAPTA, or mitofusin 2 (Mfn2)-specific short interfering RNA (siRNA). The migration, proliferation, mitochondrial morphology, membrane potential, and adenosine triphosphate production were measured. The carotid artery wire injury procedure was performed in male TRPV1 knockout mice and C57BL/6J wild-type (WT) mice that were then treated with or without Mfn2 siRNA. The re-endothelialization and neointimal formation were evaluated. RESULTS: Capsaicin significantly enhanced the migration and proliferation of HUVECs. Both capsazepine and BAPTA abolished capsaicin-induced migration and proliferation of HUVECs. In addition, capsaicin stimulated the formation of reticular mitochondria, augmented mitochondrial membrane potential, increased adenosine triphosphate production, and upregulated Mfn2. However, these effects were attenuated by knockdown of Mfn2 with specific siRNA. Dietary capsaicin markedly accelerated re-endothelialization and inhibited neointimal formation in WT mice but not in TRPV1 knockout mice. Moreover, Mfn2 siRNA also attenuated capsaicin-induced enhancement of endothelial recovery and suppression of neointimal hyperplasia in WT mice. CONCLUSIONS: Activation of TRPV1 with capsaicin attenuates neointimal formation by accelerating re-endothelialization through upregulation of Mfn2.

Melatonin attenuates postmyocardial infarction injury via increasing Tom70 expression.

Mitochondrial dysfunction leads to reactive oxygen species (ROS) overload, exacerbating injury in myocardial infarction (MI). As a receptor for translocases in the outer mitochondrial membrane (Tom) complex, Tom70 has an unknown function in MI, including melatonin-induced protection against MI injury. We delivered specific small interfering RNAs against Tom70 or lentivirus vectors carrying Tom70a sequences into the left ventricles of mice or to cultured neonatal murine ventricular myocytes (NMVMs). At 48 h post-transfection, the left anterior descending coronary arteries of mice were permanently ligated, while the NMVMs underwent continuous hypoxia. At 24 h after ischemia/hypoxia, oxidative stress was assessed by dihydroethidium and lucigenin-enhanced luminescence, mitochondrial damage by transmission electron microscopy and ATP content, and cell apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling and caspase-3 assay. At 4 weeks after ischemia, cardiac function and fibrosis were evaluated in mice by echocardiography and Masson's trichrome staining, respectively. Ischemic/hypoxic insult reduced Tom70 expression in cardiomyocytes. Tom70 downregulation aggravated post-MI injury, with increased mitochondrial fragmentation and ROS overload. In contrast, Tom70 upregulation alleviated post-MI injury, with improved mitochondrial integrity and decreased ROS production. PGC-1α/Tom70 expression in ischemic myocardium was increased with melatonin alone, but not when combined with luzindole. Melatonin attenuated post-MI injury in control but not in Tom70-deficient mice. N-acetylcysteine (NAC) reversed the adverse effects of Tom70 deficiency in mitochondria and cardiomyocytes, but at a much higher concentration than melatonin. Our findings showed that Tom70 is essential for melatonin-induced protection against post-MI injury, by breaking the cycle of mitochondrial impairment and ROS generation.

Novel role of silent information regulator 1 in acute endothelial cell oxidative stress injury.

Silent information regulator 1 (SIRT1), a class III histone deacetylase, retards aging and plays roles in cellular oxidative stress injury (OSI). However, the biological context in which SIRT1 promotes oxidative injury is not fully understood. Here, we show that SIRT1 essentially mediates hydrogen peroxide (H2O2)-induced cytotoxicity in human umbilical vein endothelial cell (HUVEC). In HUVECs, SIRT1 protein expression was significantly increased in a dose-dependent manner after H2O2 treatment, whereas the acetylation levels of the NF-κB p65 subunit and p53 were decreased. EX527 (a specific SIRT1 inhibitor) conferred protection to the HUVECs against H2O2, as indicated by an improved cell viability, adhesion, an enhanced migratory ability, a decreased apoptotic index, decreased reactive oxygen species (ROS) production and reductions in several biochemical parameters. Immunofluorescence and Western blot analyses demonstrated that H2O2 treatment up-regulated SIRT1, phosphorylated-JNK (p-JNK), p-p38MAPK, and p-ERK expression. EX527 pretreatment reversed these effects on SIRT1, p-JNK, and p-p38MAPK but further increased the p-ERK levels. Similar results were confirmed in SIRT1 siRNA experiments. In summary, SIRT1 signaling pathway inhibition imparts protection against acute endothelial OSI, and modulation of MAPKs (JNK, p38MAPK, and ERK) may be involved in the protective effect of SIRT1 inhibition.

Increased myocardial ischemia-reperfusion injury in renal failure involves cardiac adiponectin signal deficiency.

Plasma levels of adiponectin (APN) are significantly increased in patients with renal dysfunction and are inversely related to the risk of cardiovascular mortality. The present study was designed to determine the role of APN in myocardial ischemia-reperfusion (MI/R) injury in mice with renal failure and delineate the underlying mechanisms. Renal failure was induced by subtotal nephrectomy (SN). Human recombinant globular domain of adiponectin (gAd) or full-length adiponectin (fAd) was administered via intraperitoneal injection once daily for 7 consecutive days after SN, and in vivo MI/R was introduced 3 wk later. Both plasma and urinary levels of APN increased significantly in SN mice. Compared with sham-operated mice, cardiac function was significantly depressed, and myocardial infarct size and apoptosis increased in SN mice following MI/R. The aggravated MI/R injury was further intensified in APN-knockout mice and markedly ameliorated by treatment with gAd but not fAd. Moreover, SN increased myocardial NO metabolites, superoxide, and their cytotoxic reaction product peroxynitrite, upregulated inducible NO synthase expression, and decreased endothelial NOS phosphorylation. In addition, SN mice also exhibited reduced APN receptor-1 (AdipoR1) expression and AMPK activation. All these changes were further amplified in the absence of APN but reversed by gAd treatment. The present study demonstrates that renal dysfunction increases cardiac susceptibility to ischemic-reperfusion injury, which is associated with downregulated APN/AdipoR1/AMPK signaling and increased oxidative/nitrative stress in local myocardium, and provides the first evidence for the protective role of exogenous supplement of gAd on MI/R outcomes in renal failure.

Melatonin receptor-mediated protection against myocardial ischemia/reperfusion injury: role of SIRT1.

Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion (MI/R) injury by reducing oxidative stress. Activation of silent information regulator 1 (SIRT1) signaling also reduces MI/R injury. We hypothesize that melatonin may protect against MI/R injury by activating SIRT1 signaling. This study investigated the protective effect of melatonin treatment on MI/R heart and elucidated its potential mechanisms. Rats were exposed to melatonin treatment in the presence or the absence of the melatonin receptor antagonist luzindole or SIRT1 inhibitor EX527 and then subjected to MI/R operation. Melatonin conferred a cardioprotective effect by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase release, upregulating SIRT1, Bcl-2 expression and downregulating Bax, caspase-3 and cleaved caspase-3 expression. Melatonin treatment also resulted in reduced myocardium superoxide generation, gp91(phox) expression, malondialdehyde level, and increased myocardium superoxide dismutase (SOD) level, which indicate that the MI/R-induced oxidative stress was significantly attenuated. However, these protective effects were blocked by EX527 or luzindole, indicating that SIRT1 signaling and melatonin receptor may be specifically involved in these effects. In summary, our results demonstrate that melatonin treatment attenuates MI/R injury by reducing oxidative stress damage via activation of SIRT1 signaling in a receptor-dependent manner.

Diagnosis and treatment of coronary spasm in China: a case report.

Background: Coronary vasospasm (CVS) is a common cardiovascular condition, yet its implications should not be underestimated. Regrettably, the current diagnostic and treatment standards for CVS in China are not standardized, severely affecting the quality of life for patients with this condition. Case presentation: A 68-year-old male presented to the hospital one month prior due to recurrent chest pain. Coronary angiography (CAG) revealed a mid-segment muscle bridge with plaque formation in the left anterior descending artery, followed by pharmacological balloon angioplasty. The primary diagnosis post-operation was acute non-ST elevation myocardial infarction (NSTEMI) and coronary artery myocardial bridging. This time, the patient experienced nocturnal chest pain with a dynamic increase in troponin levels. Emergency CAG showed the left anterior descending and right coronary arteries were fine, with segmental narrowing reaching 95%-99%. Intravascular ultrasound (IVUS) indicated negative remodeling of the mid-segment lumen associated with myocardial bridging, with the smallest lumen area being 2.19 mm2. After intracoronary administration of nitroglycerin, the original most narrowed lumen area increased to 8.81 mm2. Consequently, a definitive diagnosis of CVS with coronary artery myocardial bridging was made, and the medication treatment plan was promptly adjusted. The patient's symptoms disappeared, and he was discharged. Follow-up after more than three months showed no recurrence of symptoms. Conclusion: In cases where provocative agents are contraindicated, CAG combined with IVUS can optimize the differential diagnosis of CVS. There is an urgent need in China to improve epidemiological data on CVS and establish standardized diagnostic and treatment protocols.

Disruption of BACH1 Protects AC16 Cardiomyocytes Against Hypoxia/Reoxygenation-Evoked Injury by Diminishing CDKN3 Transcription.

Reperfusion after myocardial infarction (MI) can lead to myocardial ischemia/reperfusion (I/R) damage. The transcription factor (TF) broad-complex, tramtrack, and bric-a-brac (BTB) and cap'n'collar (CNC) homology 1 (BACH1) is implicated in the injury. However, the downstream mechanisms of BACH1 in affecting myocardial hypoxia/reoxygenation (H/R) damage are still fully understood. AC16 cells were stimulated with H/R conditions to model cardiomyocytes under H/R. mRNA analysis was performed by quantitative real-time PCR. Protein levels were gauged by immunoblot analysis. The effect of BACH1/cyclin-dependent kinase inhibitor 3 (CDKN3) on H/R-evoked injury was assessed by measuring cell viability via Cell Counting Kit-8 (CCK-8), apoptosis (flow cytometry and caspase 3 activity), ferroptosis via Fe2+, glutathione (GSH), reactive oxygen species (ROS) and malondialdehyde (MDA) markers and inflammation cytokines interleukin-1beta (IL-1ß) and tumor necrosis factor alpha (TNF-α). The BACH1/CDKN3 relationship was examined by chromatin immunoprecipitation (ChIP) experiment and luciferase assay. BACH1 was increased in MI serum and H/R-stimulated AC16 cardiomyocytes. Functionally, disruption of BACH1 mitigated H/R-evoked in vitro apoptosis, ferroptosis and inflammation of AC16 cardiomyocytes. Mechanistically, BACH1 activated CDKN3 transcription and enhanced CDKN3 protein expression in AC16 cardiomyocytes. Our rescue experiments validated that BACH1 disruption attenuated H/R-evoked AC16 cardiomyocyte apoptosis, ferroptosis and inflammation by downregulating CDKN3. Additionally, BACH1 disruption could activate the adenosine monophosphate-activated protein kinase (AMPK) signaling by downregulating CDKN3 in H/R-stimulated AC16 cardiomyocytes. Our study demonstrates that BACH1 activates CDKN3 transcription to induce H/R-evoked damage of AC16 cardiomyocytes partially via AMPK signaling.

Research progress of drug eluting balloon in arterial circulatory system.

The arterial circulatory system diseases are common in clinical practice, and their treatment options have been of great interest due to their high morbidity and mortality. Drug-eluting balloons, as a new type of endovascular interventional treatment option, can avoid the long-term implantation of metal stents and is a new type of angioplasty without stents, so drug-eluting balloons have better therapeutic effects in some arterial circulatory diseases and have been initially used in clinical practice. In this review, we first describe the development, process, and mechanism of drug-eluting balloons. Then we summarize the current studies on the application of drug-eluting balloons in coronary artery lesions, in-stent restenosis, and peripheral vascular disease. As well as the technical difficulties and complications in the application of drug-eluting balloons and possible management options, in order to provide ideas and help for future in-depth studies and provide new strategies for the treatment of more arterial system diseases.

The Profiles of Venous Thromboembolism at Different High Altitudes.

Xiong, Shiqiang, Jun Hou, Haixia Yang, Meiting Gong, Xin Ma, Xuhu Yang, Hongyang Zhang, Yao Ma, Liang Gao, and Haifeng Pei. The profiles of venous thromboembolism at different high altitudes High Alt Med Biol. 25:223-225, 2024.-This study investigated the incidence of venous thromboembolism (VTE) in high altitude (HA) and very HA areas. Patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) diagnosed between 2004 and 2022 in Yecheng, China, were retrospectively analyzed. The results showed that patients with PE at very HA had a higher risk of lower extremity DVT (OR 16.3 [95% CI 1.2-223.2], p = 0.036), than those at HA, especially in the early stages of very HA entry, and the harsh environment of very HA further exacerbated the risk of VTE. These findings emphasize the higher risk of PE development in very HA and the need for enhanced prevention and treatment in this area.

Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy: A case report.

BACKGROUND: Bradycardia-induced cardiomyopathy (BIC), which is a disease resulting from bradycardia, is characterized by cardiac chamber enlargement and diminished cardiac function. The correction of bradycardia can allow for significant improvements in both cardiac function and structure; however, this disease has been infrequently documented. In this case, we conducted a longitudinal follow-up of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention. CASE SUMMARY: A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7. Since she had no obvious symptoms, she did not receive any treatment to improve her bradycardia during the 42-year follow-up, except for the implantation of a temporary pacemaker during labor induction surgery. As time progressed, the patient's heart gradually expanded due to her low ventricular rate, and she was diagnosed with BIC. In 2014, the patient developed atrial fibrillation, her ventricular rate gradually increased, and her heart shape gradually returned to normal. This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years, introduces another possible outcome of BIC, and emphasizes the importance of early intervention in treating BIC. CONCLUSION: BIC can induce atrial fibrillation, causing an increased ventricular rate and leading to positive cardiac remodeling.

Monascus pigment-protected bone marrow-derived stem cells for heart failure treatment.

Mesenchymal stem cells (MSCs) have demonstrated significant therapeutic potential in heart failure (HF) treatment. However, their clinical application is impeded by low retention rate and low cellular activity of MSCs caused by high inflammatory and reactive oxygen species (ROS) microenvironment. In this study, monascus pigment (MP) nanoparticle (PPM) was proposed for improving adverse microenvironment and assisting in transplantation of bone marrow-derived MSCs (BMSCs). Meanwhile, in order to load PPM and reduce the mechanical damage of BMSCs, injectable hydrogels based on Schiff base cross-linking were prepared. The PPM displays ROS-scavenging and macrophage phenotype-regulating capabilities, significantly enhancing BMSCs survival and activity in HF microenvironment. This hydrogel demonstrates superior biocompatibility, injectability, and tissue adhesion. With the synergistic effects of injectable, adhesive hydrogel and the microenvironment-modulating properties of MP, cardiac function was effectively improved in the pericardial sac of rats. Our results offer insights into advancing BMSCs-based HF therapies and their clinical applications.

Notch1 cardioprotection in myocardial ischemia/reperfusion involves reduction of oxidative/nitrative stress.

Oxidative/nitrative stress plays an important role in myocardial ischemia/reperfusion (MI/R) injury. Notch1 participates in the regulation of cardiogenesis and cardiac response to hypertrophic stress, but the function of Notch1 signaling in MI/R has not been explored. This study aims to determine the role of Notch1 in MI/R, and investigate whether Notch1 confers cardioprotection. Notch1 specific small interfering RNA (siRNA, 20 µg) or Jagged1 (a Notch ligand, 12 µg) was delivered through intramyocardial injection. 48 h after injection, mice were subjected to 30 min of myocardial ischemia followed by 3 h (for cell apoptosis and oxidative/nitrative stress), 24 h (for infarct size and cardiac function), or 2 weeks (for cardiac fibrosis and function) of reperfusion. Cardiac-specific Notch1 knockdown resulted in significantly aggravated I/R injury, as evidenced by enlarged infarct size, depressed cardiac function, increased myocardial apoptosis and cardiac fibrosis. Downregulation of Notch1 increased expression of inducible NO synthase (iNOS) and gp(91phox), enhanced the production of NO metabolites and superoxide, as well as their cytotoxic reaction product peroxynitrite. Moreover, Notch1 blockade also reduced phosphorylation of endothelial NO synthase (eNOS) and Akt, and increased expression of PTEN, a key phosphatase involved in the regulation of Akt phosphorylation. In addition, activation of Notch1 by Jagged1 or administration of peroxynitrite scavenger reduced production of peroxynitrite and attenuated MI/R injury. These data indicate that Notch1 signaling protects against MI/R injury partly though PTEN/Akt mediated anti-oxidative and anti-nitrative effects.

Cardiac-derived adiponectin induced by long-term insulin treatment ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic mice via AMPK signaling.

Type 1 diabetes (T1DM) portends poor prognosis concerning ischemic heart disease. Adiponectin (APN), an adipocytokine possessing insulin sensitizing and metabolic regulatory effects, has been recognized as a potent cardioprotective molecule. However, the relationship between APN and T1DM remains controversial and the role of cardiac-derived APN in T1DM is unclear. This study is aimed to investigate the dynamic change of both plasma and cardiac-derived APN expressions in T1DM, and the particular role of cardiac-derived APN in T1DM against myocardial ischemia/reperfusion (MI/R) injury. T1DM was established via intraperitoneal injection of streptozocin and followed by twice-daily subcutaneous injection of insulin or vehicle for 14 days. Non-diabetic mice of wild type and APN knockout were subjected to insulin or vehicle injection. MI/R was induced in Langendorff-perfused hearts. Compared to non-diabetic mice, plasma APN levels of diabetic mice significantly increased at 7 days, and slightly decreased at 14 days, while cardiac-derived APN levels gradually decreased over time. The MI/R injury measured as infarct size and cardiomyocyte apoptosis nearly doubled in diabetic mice. 14 days of insulin treatment increased both plasma and cardiac-derived APN levels in diabetic mice and attenuated myocardial injury via increasing AMPK phosphorylation in T1DM, which was partly reversed by Compound C (an AMPK inhibitor). Moreover, APN deficiency aggravated MI/R injury and partly abolished the protective effect of insulin treatment against MI/R injury, which was associated with decreased AMPK phosphorylation. The results suggest that cardiac-derived APN stimulated by long-term insulin treatment in T1DM exerts cardioprotection against MI/R injury via myocardial AMPK activation.

Impact of pre-procedural diastolic blood pressure on major adverse cardiovascular events in non ST-segment elevation myocardial infarction patients following revascularization.

Previous reports have observed a consistent J-shaped relationship between cardiac events and diastolic blood pressure (DBP). However, the EPHESUS study clearly showed that myocardial reperfusion abolished the J-shaped association, suggesting a different association pattern after revascularization. Therefore, in this study, we investigated the different patterns in which DBP affects cardiovascular risk in non ST-segment elevation myocardial infarction (NSTEMI) patients after revascularization, which may benefit the risk stratification for NSTEMI patients. We obtained the NSTEMI database from the Dryad data repository and analyzed the association between preprocedural DBP and long-term major adverse cardiovascular events (MACEs) in 1486 patients with NSTEMI following percutaneous coronary intervention (PCI). Multivariate regression models were used to assess the impact of DBP on outcomes in an adjusted fashion according to DBP tertiles. The p value for the trend was calculated using linear regression. When examined as a continuous variable, a multivariate regression analysis was repeated. Pattern stability was verified by interaction and stratified analyses. The median (interquartile range) age of the patients was 61.00 (53.00-68.00) years, and 63.32% were male. Cardiac death showed a graded increase as the DBP tertile increased (p for trend = 0.0369). When examined as a continuous variable, a 1 mmHg increase in DBP level was associated with an 18% higher risk of long-term cardiac death (95% CI: 1.01-1.36, p = 0.0311) and a 2% higher risk of long-term all-cause death (95% CI: 1.01-1.04; p = 0.0178). The association pattern remained stable when stratified by sex, age, diabetes, hypertension, and smoking status. An association between low DBP and higher cardiovascular risk was not observed in our study. We showed that higher preprocedural DBP increased the risk of long-term cardiac death and all-cause death in patients with NSTEMI following PCI.

Exploring the ECG "6+2" Phenomenon in Coronary Artery Disease and Coronary Artery Spasm: A Case Report Analysis and Treatment Implications.

BACKGROUND Although coronary artery disease and coronary artery spasm (CAS) can lead to acute myocardial infarction, there are clear differences in treatment between coronary heart disease and CAS, and the therapeutic schedule should not be confused. Furthermore, electrocardiogram (ECG) "6+2" phenomenon is recommend as a specific ECG indicator for lesions in the left main coronary artery or multiple vessels. Currently, no reports of this phenomenon in CAS exist. CASE REPORT A 72-year-old man had history of recurrent chest pain for over 6 years, with episodes lasting about 10 min and resolving with rest. He experienced symptom recurrence and exacerbation due to substance abuse. He was admitted to our Emergency Department for chest pain at rest. His emergency ECG revealed a 6+2 phenomenon, accompanied by troponin levels exceeding 18 times the reference value. Promptly, we conducted coronary angiography, with unexpected normal findings. Following thorough assessment, we postulated the patient could have CAS. Subsequent to medical team intervention, the patient's ECG normalized, leading to his discharge upon condition stabilization. CONCLUSIONS We report a case of CAS in a patient with ECG 6+2 phenomenon, without significant coronary artery stenosis. This differs from transient ST-segment elevation on ECG, a well-recognized hallmark of CAS; however, such a presentation has not been documented before. Additionally, treatment strategies for myocardial ischemic conditions stemming from coronary atherosclerosis diverge from those employed for CAS. Therefore, clinicians should advocate for coronary angiography whenever feasible. This approach serves to elucidate the underlying disease etiology and facilitates the administration of precision-targeted interventions for patients.

Pathological Roles of Oxidative Stress in Cardiac Microvascular Injury.

Cardiac microvascular injury can be a fundamental pathological process that causes high incidence cardiovascular diseases such heart failure, diabetic cardiomyopathy, and hypertension. It is also an independent risk factor for cardiovascular disease. Oxidative stress is a significant pathological process in which the body interferes with the balance of the endogenous antioxidant defense system by producing reactive oxygen species, leading to property changes and dysfunction. It has been demonstrated that oxidative stress is one of the major causes of cardiac microvascular disease. Therefore, additional investigation into the relationship between oxidative stress and cardiac microvascular injury will direct clinical management in the future. In order to give suggestions and support for future in-depth studies, we give a basic overview of the cardiac microvasculature in relation to physiopathology in this review. We also summarize the role of oxidative stress of mitochondrial and non-mitochondrial origin in cardiac microvascular injury and related drug studies.

Oxidative Stress Signaling Mediated Pathogenesis of Diabetic Cardiomyopathy.

As a serious cardiovascular complication, diabetic cardiomyopathy (DCM) refers to diabetes-related changes in myocardial structure and function, which is obviously different from those cardiomyopathy secondary to hypertension, coronary heart disease, and valvular disease. The clinical features of DCM are left ventricular hypertrophy, myocardial fibrosis, and impaired diastolic function. DCM will lead to cardiac dysfunction, eventually progress to cardiac arrhythmia, heart failure, and sudden cardiac death. At present, the pathogenesis of DCM is complex and not fully elucidated, and oxidative stress (OS), inflammatory response, glucolipid metabolism disorder, etc., are considered as the potential pathophysiological mechanisms. As a consequence, there is no specific and effective treatment for DCM. OS refers to the imbalance between reactive oxygen species (ROS) accumulation and scavenging, oxidation, and antioxidants in vivo, which is widely studied in DCM. Numerous studies have pointed out that regulating the OS signaling pathways and reducing the generation and accumulation of ROS are potential directions for the treatment of DCM. This review summarizes the major OS signaling pathways that are related to the pathogenesis of DCM, providing ideas about further research and therapy.