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Abstract Ischemia with non-obstructive coronary artery (INOCA) is a common cause of hospital admissions, leading to negative outcomes and reduced quality of life. Central to its pathophysiology is endothelial dysfunction, which contributes to myocardial ischemia despite the absence of significant coronary artery blockage. Addressing endothelial dysfunction is essential in managing INOCA to alleviate symptoms and prevent cardiovascular events. Recent studies have identified diabetes mellitus (DM) as a significant factor exacerbating INOCA complications by promoting endothelial impairment and coronary microvascular dysfunction. MicroRNAs (miRNAs) have emerged as potential biomarkers and therapeutic targets in various biological processes, including endothelial dysfunction and cardiovascular diseases. However, research on miRNA biomarkers in INOCA patients is sparse. In this study, we examined a panel of circulating miRNAs involved in the regulation of endothelial function in INOCA patients with and without DM. We analyzed miRNA expression using RT-qPCR in a cohort of consecutive INOCA patients undergoing percutaneous coronary intervention. We detected a significant dysregulation of miR-363-5p and miR-92a-3p in INOCA patients with DM compared to those without DM, indicating their role as biomarkers for predicting and monitoring endothelial dysfunction in INOCA patients with DM.

As respiratory syncytial virus (RSV) vaccine distribution gains traction in Europe and Italy, healthcare workers (HCWs) can strategize about vaccine promotion to increase uptake among patients at risk of RSV consequences, such cardiac patients. This cross-sectional survey investigated the knowledge about and attitude towards RSV and RSV vaccines, and the intention to recommend vaccination within a cardiological hospital in Italy. To explore factors associated with the outcomes of interest, multivariate logistic regression analyses were conducted. Of 197 invited HCWs, 78.2% returned the survey. The knowledge about market authorisation for new RSV vaccines for older adults (present in 46.9% of respondents) was significantly associated with the HCWs’ age, education, and previous update on vaccinations. HCWs with a higher educational level and those with a positive attitude towards RSV vaccines safety reported a higher attitude towards the importance of vaccinating people at risk. The willingness of recommending RSV vaccination to patients (70.5% of respondents) was more likely in HCWs who were knowledgeable about market authorisation for RSV vaccines and in physicians. This tempestive research sheds light on current factors influencing the strategies of cardiac HCWs regarding RSV vaccination. The results suggest the need for training events on the protective role of RSV vaccination in cardiac patients.

Background and Objectives: Cardiac patients are particularly at risk of herpes zoster (HZ), which is associated with a higher risk of major cardiovascular events. This research aimed to analyze the knowledge, attitudes and practices towards recombinant zoster vaccine (RZV) among cardiac healthcare professionals (HPs). Materials and Methods: A cross-sectional survey was conducted in a cardiological hospital in Italy. Multivariate regression models were built to identify factors associated with the outcomes of interest. Results: The response rate was 78.2% (154/197). Overall, age > 50 years and immunosuppression were recognized as risk factors for HZ by 38.3% and 75.3% of respondents, respectively. Regarding RZV, 29.1% of the HPs correctly responded about its schedule and 57.6% about the possibility of administration in immunocompromised individuals. This knowledge was significantly higher in HPs with a higher educational level (odds ratio (OR) = 4.42; 95%CI 1.70–11.47), in those who knew that HZ could cause postherpetic neuralgia (OR = 2.56; 95%CI 1.05–6.25) or major cardiovascular events (OR = 4.23; 95%CI 1.50–11.91), in those who had participated in professional updates on vaccinations (OR = 3.86; 95%CI 1.51–9.87) and in those who stated the need for further information about the RZV (OR = 6.43; 95%CI 1.42–29.98). Younger HPs (coefficient (β) = −0.02; 95%CI −0.04–−0.01), those with a positive attitude toward RZV safety (β = 2.92; 95%CI 2.49–3.36) and those who had previously cared for patients with HZ (β = 0.45; 95%CI 0.03–0.88) reported a more positive attitude toward RZV effectiveness. The practice of recommending vaccination was more prevalent in younger HPs (OR = 0.94; 95%CI 0.89–0.99), in those who had a master’s degree or higher education (OR = 7.21; 95%CI 1.44–36.08), in those with more positive attitudes toward RZV effectiveness (OR = 7.17; 95%CI 1.71–30.03) and in HPs who had already recommended the vaccine to patients in the past (OR = 4.03; 95%CI 1.08–14.96). Conclusions: Despite being a single-center study, our research brings attention to factors that currently impact cardiac HPs’ approaches to RZV. The findings indicate potential measures to enhance HPs’ awareness and practices, ultimately aiming to improve vaccination adherence and reduce the burden associated with HZ.

Life expectancy has gradually grown over the last century. This has deeply affected healthcare costs, since the growth of an aging population is correlated to the increasing burden of chronic diseases. This represents the interesting challenge of how to manage patients with chronic diseases in order to improve health care budgets. Effective primary prevention could represent a promising route. To this end, precision, together with personalized medicine, are useful instruments in order to investigate pathological processes before the appearance of clinical symptoms and to guide physicians to choose a targeted therapy to manage the patient. Cardiovascular and neurodegenerative diseases represent suitable models for taking full advantage of precision medicine technologies applied to all stages of disease development. The availability of high technology incorporating artificial intelligence and advancement progress made in the field of biomedical research have been substantial to understand how genes, epigenetic modifications, aging, nutrition, drugs, microbiome and other environmental factors can impact health and chronic disorders. The aim of the present review is to address how precision and personalized medicine can bring greater clarity to the clinical and biological complexity of these types of disorders associated with high mortality, involving tremendous health care costs, by describing in detail the methods that can be applied. This might offer precious tools for preventive strategies and possible clues on the evolution of the disease and could help in predicting morbidity, mortality and detecting chronic disease indicators much earlier in the disease course. This, of course, will have a major effect on both improving the quality of care and quality of life of the patients and reducing time efforts and healthcare costs.

Despite the availability of several therapies for the management of blood glucose in diabetic patients, most of the treatments do not show benefits on diabetic cardiomyopathy, while others even favor the progression of the disease. New pharmacological targets are needed that might help the management of diabetes and its cardiovascular complications at the same time. GRK2 appears a promising target, given its established role in insulin resistance and in systolic heart failure. Using a custom peptide inhibitor of GRK2, we assessed in vitro in L6 myoblasts the effects of GRK2 inhibition on glucose extraction and insulin signaling. Afterwards, we treated diabetic male mice (db/db) for 2 weeks. Glucose tolerance (IGTT) and insulin sensitivity (ITT) were ameliorated, as was skeletal muscle glucose uptake and insulin signaling. In the heart, at the same time, the GRK2 inhibitor ameliorated inflammatory and cytokine responses, reduced oxidative stress, and corrected patterns of fetal gene expression, typical of diabetic cardiomyopathy. GRK2 inhibition represents a promising therapeutic target for diabetes and its cardiovascular complications.

Activation of Ca2+/Calmodulin protein kinase II (CaMKII) is an important step in signaling of cardiac hypertrophy. The molecular mechanisms by which CaMKII integrates with other pathways in the heart are incompletely understood. We hypothesize that CaMKII association with extracellular regulated kinase (ERK), promotes cardiac hypertrophy through ERK nuclear localization.In H9C2 cardiomyoblasts, the selective CaMKII peptide inhibitor AntCaNtide, its penetratin conjugated minimal inhibitory sequence analog tat-CN17β, and the MEK/ERK inhibitor UO126 all reduce phenylephrine (PE)-mediated ERK and CaMKII activation and their interaction. Moreover, AntCaNtide or tat-CN17β pretreatment prevented PE induced CaMKII and ERK nuclear accumulation in H9C2s and reduced the hypertrophy responses. To determine the role of CaMKII in cardiac hypertrophy in vivo, spontaneously hypertensive rats were subjected to intramyocardial injections of AntCaNtide or tat-CN17β. Left ventricular hypertrophy was evaluated weekly for 3 weeks by cardiac ultrasounds. We observed that the treatment with CaMKII inhibitors induced similar but significant reduction of cardiac size, left ventricular mass, and thickness of cardiac wall. The treatment with CaMKII inhibitors caused a significant reduction of CaMKII and ERK phosphorylation levels and their nuclear localization in the heart.These results indicate that CaMKII and ERK interact to promote activation in hypertrophy; the inhibition of CaMKII-ERK interaction offers a novel therapeutic approach to limit cardiac hypertrophy.

Cancer development and chemo-resistance are often due to impaired functioning of the p53 tumor suppressor through genetic mutation or sequestration by other proteins. In glioblastoma multiforme (GBM), p53 availability is frequently reduced because it binds to the Murine Double Minute-2 (MDM2) oncoprotein, which accumulates at high concentrations in tumor cells. The use of MDM2 inhibitors that interfere with the binding of p53 and MDM2 has become a valid approach to inhibit cell growth in a number of cancers; however little is known about the efficacy of these inhibitors in GBM. We report that a new small-molecule inhibitor of MDM2 with a spirooxoindolepyrrolidine core structure, named ISA27, effectively reactivated p53 function and inhibited human GBM cell growth in vitro by inducing cell cycle arrest and apoptosis. In immunoincompetent BALB/c nude mice bearing a human GBM xenograft, the administration of ISA27 in vivo activated p53, inhibited cell proliferation and induced apoptosis in tumor tissue. Significantly, ISA27 was non-toxic in an in vitro normal human cell model and an in vivo mouse model. ISA27 administration in combination with temozolomide (TMZ) produced a synergistic inhibitory effect on GBM cell viability in vitro, suggesting the possibility of lowering the dose of TMZ used in the treatment of GBM. In conclusion, our data show that ISA27 releases the powerful antitumor capacities of p53 in GBM cells. The use of this MDM2 inhibitor could become a novel therapy for the treatment of GBM patients.