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 β-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.

Vaccines constitute the most effective medications in public health as they control and prevent the spread of infectious diseases and reduce mortality. Similar to other medications, allergic reactions can occur during vaccination. While most reactions are neither frequent nor serious, anaphylactic reactions are potentially life-threatening allergic reactions that are encountered rarely, but can cause serious complications. The allergic responses caused by vaccines can stem from activation of mast cells via Fcε receptor-1 type I reaction, mediated by the interaction between immunoglobulin E (IgE) antibodies against a particular vaccine, and occur within minutes or up to four hours. The type IV allergic reactions initiate 48 h after vaccination and demonstrate their peak between 72 and 96 h. Non-IgE-mediated mast cell degranulation via activation of the complement system and via activation of the Mas-related G protein-coupled receptor X2 can also induce allergic reactions. Reactions are more often caused by inert substances, called excipients, which are added to vaccines to improve stability and absorption, increase solubility, influence palatability, or create a distinctive appearance, and not by the active vaccine itself. Polyethylene glycol, also known as macrogol, in the currently available Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines, and polysorbate 80, also known as Tween 80, in AstraZeneca and Johnson & Johnson COVID-19 vaccines, are excipients mostly incriminated for allergic reactions. This review will summarize the current state of knowledge of immediate and delayed allergic reactions in the currently available vaccines against COVID-19, together with the general and specific therapeutic considerations. These considerations include: The incidence of allergic reactions and deaths under investigation with the available vaccines, application of vaccination in patients with mast cell disease, patients who developed an allergy during the first dose, vasovagal symptoms masquerading as allergic reactions, the COVID-19 vaccination in pregnancy, deaths associated with COVID-19 vaccination, and questions arising in managing of this current ordeal. Careful vaccine-safety surveillance over time, in conjunction with the elucidation of mechanisms of adverse events across different COVID-19 vaccine platforms, will contribute to the development of a safe vaccine strategy. Allergists’ expertise in proper diagnosis and treatment of allergic reactions is vital for the screening of high-risk individuals.

While hypertension is negatively associated with coronary artery spasm (CAS), scarce data are available on diabetes mellitus in relation to CAS. In addition, outcome prediction in patients with CAS is challenging due to the lack of appropriate biomarkers. Therefore, we sought to identify the roles that gender, high-sensitivity C-reactive protein (hs-CRP), diabetes mellitus and hypertension play in CAS development and prognosis. Patients (350 women and 547 men) undergoing diagnostic coronary angiography with or without proven CAS but without obstructive stenosis were evaluated at long-term follow-up (median 102 months). Diabetic women and diabetic men with low hs-CRP levels had a low and high risk of CAS (odds ratio [OR]: 0.16, 95% confidence interval [CI]: 0.01–1.88 and OR: 5.02, 95% CI: 1.03–24.54, respectively). The ORs of CAS in both women and men with the highest hs-CRP tertile (>3 mg/L) reduced from 4.41 to 1.45 and 2.98 to 1.52, respectively, if they had diabetes mellitus, and from 9.68 to 2.43 and 2.60 to 1.75, respectively, if they had hypertension. Hypertension had a more negative effect on CAS development in diabetic than non-diabetic women, which was not observed in men. The highest hs-CRP tertile was an independent predictor of adverse outcomes. Patients with the highest hs-CRP tertile had more coronary events than patients with the lowest hs-CRP tertitle (p = 0.021, log-rank test). Diabetes mellitus contributes to CAS development in men with low hs-CRP levels, but not in women. There are negative effects of diabetes mellitus and hypertension on CAS development in patients with high hs-CRP levels and especially in women. Elevated hs-CRP level independently predicts adverse outcomes.

Garcinol, a nicotinic acetylcholine receptor (nAChR) antagonist, has recently been established as an anti-inflammation agent. However, the molecular mechanism by which garcinol suppresses inflammation in the context of acute myocardial infarction (AMI) remains unclear. Hypothesis: We hypothesized that the administration of physiological doses of garcinol in mice with isoproterenol-induced AMI decreased the effect of lipoprotein(a) (Lp(a))-induced inflammation both in vivo and in vitro via the α7-nAChRs mediated p38 mitogen-activated protein kinase (MAPK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway. We analyzed altered reactive oxygen species (ROS) generation, the production of superoxide by mitochondria, cytokine expression patterns, and the role of the p38 MAPK/NF-κB signaling pathway after Lp(a)-stimulated human ventricular cardiomyocyte AC16 cells were treated with increasing doses of garcinol. C-reactive protein (CRP), interleukin (IL)-1β, IL-6, or tumor necrosis factor (TNF)-α production were detected by enzyme-linked immunosorbent assay. The Cell Counting Kit-8 assay was used to evaluate drug cytotoxicity. Western blots and confocal fluorescence microscopy were used to determine altered expression patterns of inflammatory biomarkers. We also examined whether the therapeutic effect of garcinol in AMI was mediated in part by α7-nAChR. Lp(a)-induced inflammatory cardiomyocytes had increased expression of membrane-bound α7-nAChRs in vitro and in vivo. Low-dose garcinol did not affect cardiomyocyte viability but significantly reduced mitochondrial ROS, CRP, IL-1β, IL-6, and TNF-α production in Lp(a)-stimulated cardiomyocytes (p < 0.05). The Lp(a)-induced phosphorylation of p38 MAPKs, CamKII, and NFκB, as well as NFκB-p65 nuclear translocation, was also suppressed (p < 0.05) by garcinol, while the inhibition of p38 MAPK by the inhibitor SB203580 decreased the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK. Garcinol protected cardiomyocytes by inhibiting apoptosis and inflammation in mice with AMI. Furthermore, garcinol also enhanced the expression of microRNA-205 that suppressed the α7-nAChR-induced p38 MAPK/NF-κB signaling pathway. Garcinol suppresses Lp(a)-induced oxidative stress and inflammatory cytokines by α7-nAChR-mediated inhibition of p38 MAPK/NF-κB signaling in cardiomyocyte AC16 cells and isoproterenol-induced AMI mice.

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.

Although asthma increases the risk of cardiovascular disease, little is known about the relation of asthma and its severity to coronary vasospastic angina (CVsA). We hypothesized that asthma contributed to the development of CVsA. Patients in this population-based cohort study were retrospectively collected from the Taiwan National Health Insurance database. Using propensity score matching, subjects were stratified at a 1 : 4 ratio into a study group comprising 3087 patients with a diagnosis of CVsA, and a control group consisting of 12,348 patients who underwent coronary intervention for obstructive coronary artery disease (CAD) during the period 2000 to 2011. Asthma significantly increased the risk of new-onset CVsA independent of other comorbidities [adjusted odds ratio (OR) = 1.85, 95% confidence interval (95% CI) = 1.47–2.32, P < 0.001]. In addition, the risk of new-onset CVsA was significantly higher in previous users of oral or inhaled corticosteroids (oral corticosteroids: OR = 1.22, 95% CI = 1.01–1.49, P = 0.04; inhaled corticosteroids: OR = 1.89, 95% CI = 1.28–2.79, P = 0.001). In addition, the prevalence of asthma was highest among patients with CVsA alone, followed by patients with CAD and CVsA and patients who underwent coronary intervention for CAD alone (P trend < 0.001). Our study suggests that asthma is independently associated with CVsA and prior steroid use increases the risk of CVsA development.