Publisher Correction: Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice.

In this Letter, affiliation number 1 was originally missing from the HTML; the affiliations were missing for author Ming-Yow Hung in the HTML; and the Fig. 4 legend erroneously referred to panels a-h, instead of a-g. These errors have been corrected online.

Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice.

Oxidized phospholipids (OxPL) are ubiquitous, are formed in many inflammatory tissues, including atherosclerotic lesions, and frequently mediate proinflammatory changes 1 . Because OxPL are mostly the products of non-enzymatic lipid peroxidation, mechanisms to specifically neutralize them are unavailable and their roles in vivo are largely unknown. We previously cloned the IgM natural antibody E06, which binds to the phosphocholine headgroup of OxPL, and blocks the uptake of oxidized low-density lipoprotein (OxLDL) by macrophages and inhibits the proinflammatory properties of OxPL2-4. Here, to determine the role of OxPL in vivo in the context of atherogenesis, we generated transgenic mice in the Ldlr-/- background that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter. E06-scFv was secreted into the plasma from the liver and macrophages, and achieved sufficient plasma levels to inhibit in vivo macrophage uptake of OxLDL and to prevent OxPL-induced inflammatory signalling. Compared to Ldlr-/- mice, Ldlr -/- E06-scFv mice had 57-28% less atherosclerosis after 4, 7 and even 12 months of 1% high-cholesterol diet. Echocardiographic and histologic evaluation of the aortic valves demonstrated that E06-scFv ameliorated the development of aortic valve gradients and decreased aortic valve calcification. Both cholesterol accumulation and in vivo uptake of OxLDL were decreased in peritoneal macrophages, and both peritoneal and aortic macrophages had a decreased inflammatory phenotype. Serum amyloid A was decreased by 32%, indicating decreased systemic inflammation, and hepatic steatosis and inflammation were also decreased. Finally, the E06-scFv prolonged life as measured over 15 months. Because the E06-scFv lacks the functional effects of an intact antibody other than the ability to bind OxPL and inhibit OxLDL uptake in macrophages, these data support a major proatherogenic role of OxLDL and demonstrate that OxPL are proinflammatory and proatherogenic, which E06 counteracts in vivo. These studies suggest that therapies inactivating OxPL may be beneficial for reducing generalized inflammation, including the progression of atherosclerosis, aortic stenosis and hepatic steatosis.

Coronary Artery Spasm-Related Heart Failure Syndrome: Literature Review.

Although heart failure (HF) is a clinical syndrome that becomes worse over time, certain cases can be reversed with appropriate treatments. While coronary artery spasm (CAS) is still underappreciated and may be misdiagnosed, ischemia due to coronary artery disease and CAS is becoming the single most frequent cause of HF worldwide. CAS could lead to syncope, HF, arrhythmias, and myocardial ischemic syndromes such as asymptomatic ischemia, rest and/or effort angina, myocardial infarction, and sudden death. Albeit the clinical significance of asymptomatic CAS has been undervalued, affected individuals compared with those with classic Heberden's angina pectoris are at higher risk of syncope, life-threatening arrhythmias, and sudden death. As a result, a prompt diagnosis implements appropriate treatment strategies, which have significant life-changing consequences to prevent CAS-related complications, such as HF. Although an accurate diagnosis depends mainly on coronary angiography and provocative testing, clinical characteristics may help decision-making. Because the majority of CAS-related HF (CASHF) patients present with less severe phenotypes than overt HF, it underscores the importance of understanding risk factors correlated with CAS to prevent the future burden of HF. This narrative literature review summarises and discusses separately the epidemiology, clinical features, pathophysiology, and management of patients with CASHF.

Relationship between Inflammation and Vasospastic Angina.

Coronary artery spasm (CAS) is a dynamic coronary stenosis causing vasospastic angina (VSA). However, VSA is a potentially lethal medical condition with multiple presentations, including sudden cardiac death. Despite investigations to explore its pathogenesis, no single mechanism has been found to explain the entire process of VSA occurrence. The roles of elevated local and systemic inflammation have been increasingly recognized in VSA. Treatment strategies to decrease local and systemic inflammation deserve further investigation.

Association between Coronary Artery Spasm and the risk of incident Diabetes: A Nationwide population-based Cohort Study.

Background: Non-diabetic coronary artery spasm (CAS) without obstructive coronary artery disease increases insulin resistance. We investigated the risk of incident type 2 diabetes (diabetes) associated with CAS. Methods: Patient records were retrospectively collected from the Taiwan National Health Insurance Research Database during the period 2000-2012. The matched cohorts consisted of 12,413 patients with CAS and 94,721 patients in the control group. Results: During the entire follow-up, the incidence of newly-diagnosed diabetes was 22.2 events per 1000 person-years in the CAS group and 13.9 events per 1000 person-years in the control group. The increased risk of CAS-related incident diabetes was observed regardless of sex and length of follow-up. The median time to incident diabetes was 2.9 and 3.5 years in the CAS and the control group (P <0.001), respectively, regardless of sex. Although age did not affect the risk of CAS-related incident diabetes, the risk was less apparent in the subgroups of male, dyslipidemia, chronic obstructive pulmonary disease, stroke, gout and medicated hypertension. However, CAS patients aged <50 years compared with patients ≥50 years had a greater risk of incident diabetes in females but not in males. Older CAS patients developed diabetes in a shorter length of time than younger patients. Conclusion: CAS is a risk factor for incident diabetes regardless of sex. However, females aged <50 years have a more apparent risk for CAS-related diabetes than old females, which is not observed in males. The median time of 2.9 years to incident diabetes warrants close follow-up.

Myocardial Ischemic Syndromes, Heart Failure Syndromes, Electrocardiographic Abnormalities, Arrhythmic Syndromes and Angiographic Diagnosis of Coronary Artery Spasm: Literature Review.

In coronary artery spasm (CAS), an excess coronary vasoconstriction causing total or subtotal vessel occlusion could lead to syncope, heart failure syndromes, arrhythmic syndromes, and myocardial ischemic syndromes including asymptomatic myocardial ischemia, stable and unstable angina, acute myocardial infarction, and sudden cardiac death. Although the clinical significance of CAS has been underrated because of the frequent absence of symptoms, affected patients appear to be at higher risk of syncope, serious arrhythmias, and sudden death than those with classic Heberden's angina pectoris. Therefore, a prompt diagnosis has important therapeutic implications, and is needed to avoid CAS-related complications. While a definitive diagnosis is based mainly on coronary angiography and provocative testing, clinical features may help guide decision-making. We perform a literature review to assess the past and current state of knowledge regarding the clinical features, electrocardiographic abnormalities and angiographic diagnosis of CAS, while a discussion of mechanisms is beyond the scope of this review.

Coronary Artery Spasm as Related to Anxiety and Depression: A Nationwide Population-Based Study.

OBJECTIVE: Anxiety and depression are risk factors for obstructive coronary artery disease (CAD), but their effects on coronary artery spasm (CAS) remain unestablished. METHODS: Patient records in this population-based study were retrospectively collected from the Taiwan National Health Insurance Research Database. Using propensity score matching, we used 1:1:1 ratio stratification into a control group of 10,325 individuals without CAS or CAD, a CAS group comprising 10,473 patients, and a CAD group comprising 10,473 patients during 2000-2012. RESULTS: The prevalence of CAS and CAD was 0.067% and 8.7%, respectively, in the general population. The prevalence of anxiety and depression diagnoses was significantly higher in patients with new-onset CAS than in those with new-onset CAD and controls without CAS/CAD, even after propensity score matching. Compared with CAD, anxiety and depression diagnoses conferred a higher risk of developing CAS (odds ratio [OR] = 2.29, 95% confidence interval [CI], 2.14-2.45, p < .001, and OR = 1.34, 95% CI, 1.08-1.66, p = .007, respectively). The association was even stronger when comparing CAS with the control group without CAD or CAS (OR = 5.20, 95% CI, 4.72-5.74, p < .001, and OR = 1.98, 95% CI, 1.50-2.62, p < .001, respectively). The increased risk of new-onset CAS as related to previous anxiety and depression diagnoses was comparable between males and females. CONCLUSIONS: Compared with CAD or the general population, anxiety and depression diagnoses confer a higher risk of developing CAS. No sex differences are found for the association of anxiety and depression with CAS.

Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease: The Copenhagen General Population Study.

OBJECTIVE: Lipoprotein(a) is causally associated with calcific aortic valve disease (CAVD). Lipoprotein(a) carries proinflammatory and procalcific oxidized phospholipids (OxPL). We tested whether the CAVD risk is mediated by the content of OxPL on lipoprotein(a). APPROACH AND RESULTS: A case-control study was performed within the Copenhagen General Population Study (n=87 980), including 725 CAVD cases (1977-2013) and 1413 controls free of cardiovascular disease. OxPL carried by apoB (apolipoprotein B-100; OxPL-apoB) or apolipoprotein(a) (OxPL-apo(a)) containing lipoproteins, lipoprotein(a) levels, LPA kringle IV type 2 repeat, and rs10455872 genetic variants were measured. OxPL-apoB and OxPL-apo(a) levels correlated with lipoprotein(a) levels among cases (r=0.75 and r=0.95; both P<0.001) and controls (r=0.65 and r=0.93; both P<0.001). OxPL-apoB levels associated with risk of CAVD with odds ratios of 1.2 (95% confidence interval [CI]:1.0-1.6) for 34th to 66th percentile levels, 1.6 (95% CI, 1.2-2.1) for 67th to 90th percentile levels, 2.0 (95% CI, 1.3-3.0) for 91st to 95th percentile levels, and 3.4 (95% CI, 2.1-5.5) for levels >95th percentile, versus levels <34th percentile (trend, P<0.001). Corresponding odds ratios for OxPL-apo(a) were 1.2 (95% CI, 1.0-1.5), 1.2(95% CI, 0.9-1.6), 2.1(95% CI, 1.4-3.1), and 2.9(95% CI, 1.9-4.5; trend, P<0.001) and were similar for lipoprotein(a). LPA genotypes associated with OxPL-apoB, OxPL-apo(a), and lipoprotein(a) levels and explained 34%, 46%, and 39%, respectively, of the total variation in levels. LPA genotypes associated with risk of CAVD; a doubling in genetically determined OxPL-apoB, OxPL-apo(a), and lipoprotein(a) levels associated with odds ratio of CAVD of 1.18 (95% CI, 1.10-1.27), 1.09 (95% CI, 1.05-1.13), and 1.09 (95% CI, 1.05-1.14), respectively, comparable to the corresponding observational estimates of 1.27 (95% CI, 1.16-1.39), 1.13 (95% CI, 1.08-1.18), and 1.11 (95% CI, 1.06-1.17). CONCLUSIONS: OxPL-apoB and OxPL-apo(a) are novel genetic and potentially causal risk factors for CAVD and may explain the association of lipoprotein(a) with CAVD.

Arterial Stiffness Index and Coronary Artery Plaques in Patients with Subclinical Coronary Atherosclerosis.

BACKGROUND: Arterial stiffness is a physiologic quantitative value used to measure arterial compliance. It is predictive of coronary atherosclerosis in patients with intermediate to high cardiovascular risk. However, a correlation between arterial stiffness and subclinical coronary atherosclerosis has yet to be established. Therefore, the purpose of this study was to evaluate arterial stiffness using an arterial stiffness index (ASI) and investigate its association with coronary artery plaque in patients with subclinical coronary atherosclerosis. METHODS: Our study enrolled 156 consecutive subjects who underwent health screening using a 64-slice cardiac computed tomography angiography (CCTA). Their arterial stiffness index was assessed noninvasively by CardioVision(®) MS-2000. The atheroma on the coronary vessel walls was analyzed. RESULTS: Of the 156 patients, 53 displayed at least one > 50% stenotic lesion over the coronary arteries in CCTA images. The patients with at least one > 50% coronary stenotic plaque were older and had higher systolic blood pressure and ASI values than patients without > 50% coronary stenotic plaque. After dividing the study population into 2 groups by those patients over and under 50 years of age, the ASI positively correlated with the presentation of at least one > 50% coronary stenotic plaque in patients aged ≥ 50 years (odds ratio = 1.02, 95% confidence interval: 1.00-1.04, p = 0.03). CONCLUSIONS: The ASI could play a role in risk stratification systems for coronary artery disease in patients with subclinical coronary atherosclerosis, and is a useful clinical marker for the correlation of early coronary plaque. KEY WORDS: Arterial stiffness; Arterial stiffness index; Atherosclerosis; Coronary artery plaque.

What is the ultimate test that lowering lipoprotein(a) is beneficial for cardiovascular disease and aortic stenosis?

PURPOSE OF REVIEW: Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD) and calcific aortic valve stenosis. We review recent studies that highlight Lp(a) in CVD and calcific aortic valve stenosis and propose pathways to clinical registration of Lp(a)-lowering agents. RECENT FINDINGS: Over the last few years, almost irrefutable evidence has accumulated that Lp(a) is a causal, independent, genetic risk factor for CVD. Most recently, new data have emerged that elevated Lp(a) is causally associated with calcific aortic valve stenosis and the need for aortic valve replacement. Three levels of evidence to support these findings: epidemiological studies, Mendelian randomization studies and genetic association studies. A dedicated Lp(a)-lowering trial has not been performed to date. Emerging Lp(a)-lowering therapies with specific and potent lowering of Lp(a) are in phase II clinical trials and provide a tool to test the hypothesis that lowering Lp(a) plasma levels will lead to clinical benefit. SUMMARY: We provide a rationale for the potential clinical use of Lp(a)-lowering therapies in high-risk patients or patients with established CVD whose major risk factor is elevated Lp(a) levels and propose clinical studies and trials to demonstrate that lowering Lp(a) levels will effectively reduce the risk of calcific aortic valve stenosis and CVD.

Coronary artery spasm: review and update.

Coronary artery spasm (CAS), an intense vasoconstriction of coronary arteries that causes total or subtotal vessel occlusion, plays an important role in myocardial ischemic syndromes including stable and unstable angina, acute myocardial infarction, and sudden cardiac death. Coronary angiography and provocative testing usually is required to establish a definitive diagnosis. While the mechanisms underlying the development of CAS are still poorly understood, CAS appears to be a multifactorial disease but is not associated with the traditional risk factors for coronary artery disease. The diagnosis of CAS has important therapeutic implications, as calcium antagonists, not ß-blockers, are the cornerstone of medical treatment. The prognosis is generally considered benign; however, recurrent episodes of angina are frequently observed. We provide a review of the literature and summarize the current state of knowledge regarding the pathogenesis of CAS.

Cardio-Oncoimmunology: Cardiac Toxicity, Cardiovascular Hypersensitivity, and Kounis Syndrome.

Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT prolongation, torsades de pointes, pericardial effusion, and hypotension, as well as chronic conditions, such as hypertension, and systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovascular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovascular side effect continues even after the causative medication is stopped, it is referred to as a cardiotoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even at very low medication dosages, and can present as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome, and myocarditis caused by cancer therapy.

"When," "Where," and "How" of SARS-CoV-2 Infection Affects the Human Cardiovascular System: A Narrative Review.

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory coronavirus-2 (SARS-CoV-2). Several explanations for the development of cardiovascular complications during and after acute COVID-19 infection have been hypothesized. The COVID-19 pandemic, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. The myocardial injury in COVID-19 patients has been associated with coronary spasm, microthrombi formation, plaque rupture, hypoxic injury, or cytokine storm, which have the same pathophysiology as the three clinical variants of Kounis syndrome. The angiotensin-converting enzyme 2 (ACE2), reninaldosterone system (RAAS), and kinin-kallikrein system are the main proposed mechanisms contributing to cardiovascular complications with the COVID-19 infection. ACE receptors can be found in the heart, blood vessels, endothelium, lungs, intestines, testes, neurons, and other human body parts. SARS-CoV-2 directly invades the endothelial cells with ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This causes angiotensin II accumulation downregulation of the ACE2 receptors, resulting in prothrombotic effects, such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. The KKS system typically causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation, but SARS-CoV-2 infection impairs such counterbalancing effects. This cascade results in cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries, microvascular disease, Kounis syndrome, prolonged COVID, myocardial fibrosis, myocarditis, new-onset hypertension, pericarditis, postural orthostatic tachycardia syndrome, pulmonary hypertension, stroke, Takotsubo syndrome, venous thromboembolism, and thrombocytopenia. In this narrative review, we describe and elucidate when, where, and how COVID-19 affects the human cardiovascular system in various parts of the human body that are vulnerable in every patient category, including children and athletes.

Gender-specific prognosis and risk impact of C-reactive protein, hemoglobin and platelet in the development of coronary spasm.

BACKGROUND: Scarce data are available on hemoglobin and platelet in relation to coronary artery spasm (CAS) development. We sought to determine the roles that high-sensitivity C-reactive protein (hs-CRP), hemoglobin and platelet play in CAS patients. METHODS: Patients (337 women and 532 men) undergoing coronary angiography with or without CAS but without obstructive coronary artery disease were evaluated during a 12-year period. RESULTS: Among women with high hemoglobin levels, the odds ratios (OR) from the lowest (<1 mg/l) to the highest tertiles (>3 mg/l) of hs-CRP were 1.21, 2.15, and 5.93 (p=0.009). In women with low hemoglobin levels, an elevated risk was found from the middle to the highest tertiles of hs-CRP (OR 0.59 to 3.85) (p=0.004). This relationship was not observed in men. In men, platelet count was the most significant risk factor for CAS (p=0.004). The highest likelihood of developing CAS was found among women with the highest hs-CRP tertile and low platelet counts (OR 8.77; 95% confidence interval [CI] 2.20-35.01) and among men with the highest hs-CRP tertile and high platelet counts (OR 4.58; 95% CI 0.48-43.97). Neither hemoglobin level nor platelet count was associated with frequent recurrent angina in both genders with CAS whereas death and myocardial infarction were rare. CONCLUSIONS: There are positive interactions among hs-CRP, hemoglobin and platelet in women with this disease, but not in men. While hemoglobin is a modifier in CAS development in women, platelet count is an independent risk factor for men. Both women and men have good prognosis of CAS.

Outcomes of Atrioventricular Node Ablation and Pacing in Patients with Heart Failure and Atrial Fibrillation: From Cardiac Resynchronization Therapy to His Bundle Pacing.

Objective: To review the relevant literature on the use of atrioventricular node ablation and pacing in patients with heart failure and atrial fibrillation. Methods: APubMed/MEDLINE and SCOPUS search was performed in order to assess the clinical outcomes of atrioventricular node ablation and pacemaker implantation, as well as the complications that may occur. Results: Several clinical trials, observational analyses and meta-analyses have shown that the "pace and ablate" strategy not only improves symptoms but also can enhance cardiac performance in patients with heart failure and atrial fibrillation. Although this procedure is effective and safe, some complications may occur including worsening of heart failure, permanent fibrillation, arrhythmias and sudden death. Regarding pacemaker implantation, cardiac resynchronization therapy is shown to be the optimal choice compared to right ventricle apical pacing. His bundle pacing is a promising alternative to cardiac resynchronization therapy and has shown beneficial effects, while left bundle branch pacing is an innovative modality. Conclusions: Atrioventricular node ablation and pacemaker implantation is shown to have beneficial effects on clinical outcomes of patients with atrial fibrillation ± heart failure who do not respond or are intolerant to medical treatment. Cardiac resynchronization therapy is the treatment of choice and His bundle pacing seems to be an effective alternative way of pacing in these patients.

Effects of COVID-19 Infection and Vaccination on the Female Reproductive System: A Narrative Review

Several studies and research papers have been published to elucidate and understand the mechanism of the coronavirus disease 2019 (COVID-19) pandemic and its long-term effects on the human body. COVID-19 affects a number of organs, including the female reproductive system. However, less attention has been given to the effects of COVID-19 on the female reproductive system due to their low morbidity. The results of studies investigating the relationship between COVID-19 infection and ovarian function in women of reproductive age have shown the harmless involvement of COVID-19 infection. Several studies have reported the involvement of COVID-19 infection in oocyte quality, ovarian function, and dysfunctions in the uterine endometrium and the menstrual cycle. The findings of these studies indicate that COVID-19 infection negatively affects the follicular microenvironment and dysregulate ovarian function. Although the COVID-19 pandemic and female reproductive health have been studied in humans and animals, very few studies have examined how COVID-19 affects the female reproductive system. The objective of this review is to summarize the current literature and categorize the effects of COVID-19 on the female reproductive system, including the ovaries, uterus, and hormonal profiles. The effects on oocyte maturation, oxidative stress, which causes chromosomal instability and apoptosis in ovaries, in vitro fertilization cycle, high-quality embryos, premature ovarian insufficiency, ovarian vein thrombosis, hypercoagulable state, women's menstrual cycle, the hypothalamus-pituitary-ovary axis, and sex hormones, including estrogen, progesterone, and the anti-Müllerian hormone, are discussed in particular.

Apolipoprotein (a)/Lipoprotein(a)-Induced Oxidative-Inflammatory α7-nAChR/p38 MAPK/IL-6/RhoA-GTP Signaling Axis and M1 Macrophage Polarization Modulate Inflammation-Associated Development of Coronary Artery Spasm.

OBJECTIVE: Apolipoprotein (a)/lipoprotein(a) (Lp(a)), a major carrier of oxidized phospholipids, and α7-nicotinic acetylcholine receptor (α7-nAChR) may play an important role in the development of coronary artery spasm (CAS). In CAS, the association between Lp(a) and the α7-nAChR-modulated inflammatory macrophage polarization and activation and smooth muscle cell dysfunction remains unknown. METHODS: We investigated the relevance of Lp(a)/α7-nAChR signaling in patient monocyte-derived macrophages and human coronary artery smooth muscle cells (HCASMCs) using expression profile correlation analyses, fluorescence-assisted cell sorting flow cytometry, immunoblotting, quantitative real-time polymerase chain reaction, and clinicopathological analyses. RESULTS: There are increased serum Lp(a) levels (3.98-fold, p = 0.011) and macrophage population (3.30-fold, p = 0.013) in patients with CAS compared with patients without CAS. Serum Lp(a) level was positively correlated with high-sensitivity C-reactive protein (r 2 = 0.48, p < 0.01), IL-6 (r 2 = 0.38, p = 0.03), and α7-nAChR (r 2 = 0.45, p < 0.01) in patients with CAS, but not in patients without CAS. Compared with untreated or low-density lipoprotein- (LDL-) treated macrophages, Lp(a)-treated macrophages exhibited markedly enhanced α7-nAChR mRNA expression (p < 0.01) and activity (p < 0.01), in vitro and ex vivo. Lp(a) but not LDL preferentially induced CD80+ macrophage (M1) polarization and reduced the inducible nitric oxide synthase expression and the subsequent NO production. While shRNA-mediated loss of α7-nAChR function reduced the Lp(a)-induced CD80+ macrophage pool, both shRNA and anti-IL-6 receptor tocilizumab suppressed Lp(a)-upregulated α7-nAChR, p-p38 MAPK, IL-6, and RhoA-GTP protein expression levels in cultures of patient monocyte-derived macrophages and HCASMCs. CONCLUSIONS: Elevated Lp(a) levels upregulate α7-nAChR/IL-6/p38 MAPK signaling in macrophages of CAS patients and HCASMC, suggesting that Lp(a)-triggered inflammation mediates CAS through α7-nAChR/p38 MAPK/IL-6/RhoA-GTP signaling induction, macrophage M1 polarization, and HCASMC activation.

Anti-Diabetic Therapy, Heart Failure and Oxidative Stress: An Update.

Diabetes mellitus (DM) and heart failure (HF) are two chronic disorders that affect millions worldwide. Hyperglycemia can induce excessive generation of highly reactive free radicals that promote oxidative stress and further exacerbate diabetes progression and its complications. Vascular dysfunction and damage to cellular proteins, membrane lipids and nucleic acids can stem from overproduction and/or insufficient removal of free radicals. The aim of this article is to review the literature regarding the use of antidiabetic drugs and their role in glycemic control in patients with heart failure and oxidative stress. Metformin exerts a minor benefit to these patients. Thiazolidinediones are not recommended in diabetic patients, as they increase the risk of HF. There is a lack of robust evidence on the use of meglinitides and acarbose. Insulin and dipeptidyl peptidase-4 (DPP-4) inhibitors may have a neutral cardiovascular effect on diabetic patients. The majority of current research focuses on sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. SGLT2 inhibitors induce positive cardiovascular effects in diabetic patients, leading to a reduction in cardiovascular mortality and HF hospitalization. GLP-1 receptor agonists may also be used in HF patients, but in the case of chronic kidney disease, SLGT2 inhibitors should be preferred.

The Effect of Long COVID-19 Infection and Vaccination on Male Fertility; A Narrative Review.

Earlier research has suggested that the male reproductive system could be particularly vulnerable to SARS-CoV-2 (COVID-19) infection, and infections involving this novel disease not only pose serious health threats but could also cause male infertility. Data from multi-organ research during the recent outbreak indicate that male infertility might not be diagnosed as a possible consequence of COVID-19 infection. Several review papers have summarized the etiology factors on male fertility, but to date no review paper has been published defining the effect of COVID-19 infection on male fertility. Therefore, the aim of this study is to review the published scientific evidence regarding male fertility potential, the risk of infertility during the COVID-19 pandemic, and the impact of COVID-19 vaccination on the male reproductive system. The effects of COVID-19 infection and the subsequent vaccination on seminal fluid, sperm count, sperm motility, sperm morphology, sperm viability, testes and sex hormones are particularly reviewed.

The Involvement of CXC Motif Chemokine Ligand 10 (CXCL10) and Its Related Chemokines in the Pathogenesis of Coronary Artery Disease and in the COVID-19 Vaccination: A Narrative Review.

Coronary artery disease (CAD) and coronary heart disease (CHD) constitute two of the leading causes of death in Europe, USA and the rest of the world. According to the latest reports of the Iranian National Health Ministry, CAD is the main cause of death in Iranian patients with an age over 35 years despite a significant reduction in mortality due to early interventional treatments in the context of an acute coronary syndrome (ACS). Inflammation plays a fundamental role in coronary atherogenesis, atherosclerotic plaque formation, acute coronary thrombosis and CAD establishment. Chemokines are well-recognized mediators of inflammation involved in several bio-functions such as leucocyte migration in response to inflammatory signals and oxidative vascular injury. Different chemokines serve as chemo-attractants for a wide variety of cell types including immune cells. CXC motif chemokine ligand 10 (CXCL10), also known as interferon gamma-induced protein 10 (IP-10/CXLC10), is a chemokine with inflammatory features whereas CXC chemokine receptor 3 (CXCR3) serves as a shared receptor for CXCL9, 10 and 11. These chemokines mediate immune responses through the activation and recruitment of leukocytes, eosinophils, monocytes and natural killer (NK) cells. CXCL10, interleukin (IL-15) and interferon (IFN-g) are increased after a COVID-19 vaccination with a BNT162b2 mRNA (Pfizer/BioNTech) vaccine and are enriched by tumor necrosis factor alpha (TNF-α) and IL-6 after the second vaccination. The aim of the present study is the presentation of the elucidation of the crucial role of CXCL10 in the patho-physiology and pathogenesis of CAD and in identifying markers associated with the vaccination resulting in antibody development.