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Prostaglandin E 2 (PGE 2 ), that plays a crucial role in angiogenesis as well as in ischemic and inflammatory disorders of the brain, is associated with breakdown of the blood-brain barrier (BBB). Previously, we had shown that PGE 2 -induced human brain endothelial cells (HBECs) migration, and works in a cooperative manner through its three receptors (EP 2 , EP 3 & EP 4 ). However, the detailed signaling mechanism of PGE 2 -induced HBECs migration remains obscure. In this present study, we investigated the signaling pathway of actin dynamics/polymerization and migration of HBECs by PGE 2 in vitro. Expression of ROCK was analyzed by ELISA and RT-PCR. Actin polymerization was evaluated by NBD-phallacidin immunofluorescence staining. HBECs expressed only ROCK II. PGE 2 (100 pM) induced ROCK II expression occurs in dose-and-time-dependent manner. ROCK II inhibition by Y27632 (150nM), as well as ROCK II silencing significantly attenuated PGE 2 -induced migration of HBECs. We further showed that pretreatment of PKA inhibitor (H-89; 0.5 μM) or adenylate cyclase inhibitor (ddA; 1μM) completely inhibited PGE 2 -induced ROCK II activity. Furthermore, PGE 2 -induced MLC phosphorylation also occurs in a time-dependent manner. However, pretreatment of ROCK II inhibitor or silencing of ROCK II significantly abrogated PGE 2 -induced MLC phosphorylation as well as F-actin polymerization. Our ex-vivo aortic ring angiogenesis study also showed that pretreatment of ROCK II inhibitor significantly inhibited ECs sprouting. These results suggest that PGE 2 -induced HBECs migration is mediated through PKA, ROCK II and MLC phosphorylation as well as F-actin polymerization, indicating that modulation of these pathways may aid in the future treatment of dysregulated angiogenesis in cerebrovascular diseases.

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury.

Cardio-oncology is a subspecialty that provides cardiac care for patients with cancer. Newer oncological agents have not only increased survivorship, but also sprouted novel cardiovascular toxicity (CVT) involving any component of the cardiovascular system, albeit with some preferential targets. Patients with cancer should undergo a baseline cardiovascular risk assessment and have individualised surveillance planned during cancer therapy and post treatment. The early diagnosis of CVT, by clinical history and examination along with imaging and laboratory analysis, is paramount. Management includes cardioprotective strategies and multidisciplinary decision-making regarding the risk–benefit ratio of oncological treatment based on CVT.

Purpose of review To understand the variety of conditions in which the pericardium may be affected in cancer patients. Recent findings Cancer may affect the pericardium directly (primary cancer; uncommon) or through metastases (commoner). Cancer treatment (chemotherapy and radiotherapy) may affect the pericardium leading to pericarditis and myopericarditis. Pericardial effusions, tamponade and constrictive pericarditis are complications that can also occur. A variety of techniques (predominantly cardiac imaging related) are used to make the diagnosis with the treatment strategy dependent on whether the pericardial disease is due to cancer or as a result of cancer treatment. Summary A variety of pericardial diseases may be caused by cancer and cancer treatment. Determining the aetiology and providing effective treatment can often be challenging.

Cancer patients face a higher risk of future myocardial infarction (MI), even after completion of anticancer therapies. MI is a critical source of physical and financial stress in noncancer patients, but its impacts associated with cancer patients also saddled with the worry (stress) of potential reoccurrence is unknown. Therefore, we aimed to quantify MI's stress and financial burden after surviving cancer and compare to those never diagnosed with cancer. Utilizing cross-sectional national survey data from 2013 to 2018 derived from publicly available United States datasets, the National Health Interview Survey , and economic data from the National Inpatient Sample , we compared the socio-economic outcomes in those with MI by cancer-status. We adjusted for social, demographic, and clinical factors. Overall, 19,504 (10.2%) of the 189,836 National Health Interview Survey responders reported having cancer for more than 1 year. There was an increased prevalence of MI in cancer survivors compared with noncancer patients (8.8% vs 3.2%, p <0.001). MI was associated with increased financial worry, food insecurity, and financial burden of medical bills (p <0.001, respectively); however, concurrent cancer did not seem to be an effect modifier (p >0.05). There was no difference in annual residual family income by cancer status; however, 3 lowest deciles of residual income representing 21.1% cancer-survivor with MI had a residual income of <$9,000. MI continues to represent an immense source of financial and perceived stress. In conclusion, although cancer patients face a higher risk of subsequent MI, this does not appear to advance their reported stress significantly.

Sterile inflammation (SI) is an inflammatory response triggered by the release of damage‐associated molecular patterns (DAMPs) from dying cells, distinct from normal inflammation in its origin from tissue injury and necrosis rather than microbial invasion. Circulating nucleic acids (CNAs), high‐mobility group box 1 (HMGB1), von Willebrand factor (vWF), and S100b protein are notable markers of SI, indicative of tissue damage and implicated in thrombotic disorders. Innate immunity, involving cells like macrophages and dendritic cells, recognizes DAMPs via pattern recognition receptors (PRRs) like Toll‐like receptors and NOD‐like receptors, initiating inflammatory signaling cascades central to SI and its cardiovascular consequences. Thrombosis, a common outcome of SI, underscores the intricate interplay between inflammation and hemostasis, with hypoxia exacerbating thrombotic risk through platelet activation and endothelial dysfunction. The established link between inflammation and thrombosis highlights the clinical significance of SI, where molecules like HMGB1, extracellular RNA (eRNA), and eDNA actively participate in thromboembolic disorders. SI’s relevance is particularly evident in COVID‐19‐induced thrombotic disorders, where dysregulated immune responses and endothelial dysfunction contribute to systemic inflammation and heightened thrombotic risk. Understanding SI’s mechanisms in these contexts is vital for developing targeted therapies to mitigate vascular complications and enhance patient outcomes in cardiovascular diseases and COVID‐19‐associated thrombosis.

Multiple myeloma (MM) is the third most common haematological malignancy, with increasing prevalence over recent years. Advances in therapy have improved survival, changing the clinical course of MM into a chronic condition and meaning that management of comorbidities is fundamental to improve clinical outcomes. Cardiovascular (CV) events affect up to 7.5% of individuals with MM, due to a combination of patient, disease and treatment-related factors and adversely impact survival. MM typically affects older people, many with pre-existing CV risk factors or established CV disease, and the disease itself can cause renal impairment, anaemia and hyperviscosity, which exacerabate these further. Up to 15% of patients with MM develop systemic amyloidosis, with prognosis determined by the extent of cardiac involvement. Management of MM generally involves administration of multiple treatment lines over several years as disease progresses, with many drug classes associated with adverse CV effects including high rates of venous and arterial thrombosis alongside heart failure. Recommendations for holistic management of patients with MM now include routine baseline risk stratification including ECG and echocardiography and administration of thromboprophylaxis drugs for patients treated with immunomodulatory drugs. Close surveillance of high-risk patients with collaboration between haematology and cardiology is required, with prompt investigation in the event of CV symptoms, in order to identify and treat complications early. Decisions regarding discontinuation of cardiotoxic therapies should be made in a multidisciplinary setting, taking into account the severity of the complication, prognosis, expected benefits and the availability of effective alternatives.

Earlier age at menarche has been associated with higher risk of coronary heart disease, but the mechanisms underlying the association remain unclear. We assessed the relationship of pubertal timing, in both men (n = 672) and women (n = 713), with vascular (carotid intima-media thickness (cIMT), pulse wave velocity (PWV)) and cardiac (left ventricular (LV) structure and function) measures recorded at age 60–64 yrs in a British birth cohort study. Regression models found that earlier menarche was associated with higher (more adverse) LV mass, LV end diastolic volume and left atrial volume, but not with other cardiac measures, cIMT or PWV. Associations were attenuated after adjustment for either adult or childhood BMI (e.g. mean difference in LV mass per year later menarche: −4.2 g (95% CI:−7.0,−1.4) reducing to −2.2 g (95% CI:−4.7,0.4) after adjustment for adult BMI). There were no associations among men, despite those fully mature at 15 yrs having higher blood pressure than the least mature group by 10.21 mmHg (95% CI:19.45,0.98). Any effect of pubertal timing on vascular and cardiac structure and function is likely to be small and primarily confounded by pre-pubertal BMI and/or mediated through adult adiposity.

More evidence-based strategies are needed for preventing and managing cancer treatment-related cardiovascular toxicity (CTR-CVT). Owing to the growing body of evidence supporting their cardioprotective role in several cardiac injury scenarios, sodium-glucose cotransporter 2 inhibitors (SGLT2i) may be beneficial for preventing and treating CTR-CVT. In October 2024, a search was conducted of the PubMed database to review full studies investigating the cardioprotective role of SGLT2i against CTR-CVT. We identified 44 full published/pre-print studies and 3 ongoing randomised controlled trial across eight types of cancer treatment (anthracyclines, platinum-containing therapy, immune checkpoint inhibitors, HER2-targeted therapies, kinase inhibitors, androgen deprivation therapies, multiple myeloma therapies and 5-fluorouracil). Most studies used animal models and focussed on primary prevention. 43 of the 44 studies found some cardioprotective effect of SGLT2i against CTR-CVT, which in some cases included preventing ejection fraction decline and aberrations in cardiac electrophysiological parameters. Some studies also observed beneficial effects on mortality. A central triad of anti-inflammatory, anti-oxidative and anti-apoptotic mechanisms likely underlie SGLT2i-mediated cardioprotection against CTR-CVT. Overall, this growing body of research suggests that SGLT2i may be a promising candidate for preventing CTR-CVT either as monotherapy or in combination with other cardioprotective drugs. However, the literature is limited in that no prospective randomised controlled trials investigating SGLT2i for the prevention and management of CTR-CVT exist and most existing human retrospective data is based on diabetic populations. Future work must focus on addressing these limitations of the current literature.

Although it is recognized that risks of cardiovascular diseases associated with heart failure develop over the life course, no studies have reported whether life course socioeconomic inequalities exist for heart failure risk. The Medical Research Council's National Survey of Health and Development was used to investigate associations between occupational socioeconomic position during childhood, early adulthood and middle age and measures of cardiac structure [left ventricular (LV) mass index and relative wall thickness (RWT)] and function [systolic: ejection fraction (EF) and midwall fractional shortening (mFS); diastolic: left atrial (LA) volume, E/A ratio and E/e' ratio)]. Different life course models were compared with a saturated model to ascertain the nature of the relationship between socioeconomic position across the life course and each cardiac marker. Findings showed that models where socioeconomic position accumulated over multiple time points in life provided the best fit for 3 of the 7 cardiac markers: childhood and early adulthood periods for the E/A ratio and E/e' ratio, and all three life periods for LV mass index. These associations were attenuated by adjustment for adiposity, but were little affected by adjustment for other established or novel cardio-metabolic risk factors. There was no evidence of a relationship between socioeconomic position at any time point and RWT, EF, mFS or LA volume index. In conclusion, socioeconomic position across multiple points of the lifecourse, particularly earlier in life, is an important determinant of some measures of LV structure and function. BMI may be an important mediator of these associations.