With coronary artery disease (CAD) projected to remain the leading cause of global mortality, prevention strategies seem to be the only effective approach able to reduce the burden and improve mortality and morbidity. At this moment, diagnostic strategies focus mainly on symptomatic patients, ignoring the occurrence of major cardiovascular events as the only manifestation of CAD. As two thirds of fatal myocardial infarction are resulting from plaque rupture, an approach based on the "vulnerable plaque" concept is mandatory in order to improve patient diagnosis, treatment, and, by default, prognosis. Given that the main studies focus on a plaque-centered approach, this is a prospective observational study that will perform a complex assessment of the features that characterize unstable coronary lesions, in terms of both local assessment via specific coronary computed tomography angiography markers of coronary plaque vulnerability and systemic approach based on serological markers of systemic inflammation in patients proved to be "vulnerable" by developing acute cardiovascular events.

Stress disorders impair sleep, quality of life, however, their pathomechanisms are unknown. Prolactin-releasing peptide (PrRP) is a stress mediator, therefore, we hypothesised that PrRP may be involved in the development of stress disorders. PrRP is produced by the medullary A1/A2 noradrenaline (NA) cells, which transmit stress signals to forebrain centers, and by non-NA cells in the hypothalamic dorsomedial nucleus. We found in male rats that both PrRP and PrRP-NA cells innervate melanin-concentrating hormone (MCH) producing neurons in the dorsolateral hypothalamus (DLH). These cells serve as a key hub for regulating sleep and affective states.Ex vivo,PrRP hyperpolarized MCH neurons and further increased the hyperpolarization caused by NA. Following sleep deprivation, intracerebroventricular PrRP injection reduced the number of REM sleep-active MCH cells. PrRP expression in the dorsomedial nucleus was up-regulated by sleep deprivation, while down-regulated by REM sleep rebound. Both in learned helplessness paradigm and after peripheral inflammation, impaired coping with sustained stress was associated with (i) overactivation of PrRP cells, (ii) PrRP protein and receptor depletion in the DLH, and (iii) dysregulation of MCH expression. Exposure to stress in PrRP insensitive period led to increased passive coping with stress. Normal PrRP signaling, therefore, seems to protect animals against stress-related disorders. PrRP signaling in the DLH is important component of the PrRP’s action, which may be mediated by MCH neurons. Moreover, PrRP receptors were downregulated in the DLH of human suicidal victims. As stress-related mental disorders are the leading cause of suicide, our findings may have particular translational relevance.SIGNIFICANCE STATEMENT:Treatment resistance to monoaminergic antidepressants is a major problem. Neuropeptides that modulate the central monoaminergic signaling are promising targets for developing alternative therapeutic strategies. We found that stress-responsive prolactin-releasing peptide (PrRP) cells innervated melanin-concentrating hormone (MCH) neurons that are crucial in the regulation of sleep and mood. PrRP inhibited MCH cell activity and enhanced the inhibitory effect evoked by noradrenaline, a classic monoamine, on MCH neurons. We observed that impaired PrRP signaling led to failure in coping with chronic/repeated stress and was associated with altered MCH expression. We found alterations of the PrRP system also in suicidal human subjects. PrRP dysfunction may underlie stress disorders, and fine-tuning MCH activity by PrRP may be an important part of the mechanism.

Atherosclerosis is the elemental precondition for any cardiovascular disease and the predominant cause of ischemic heart disease that often leads to myocardial infarction. Systemic risk factors play an important role in the starting and progression of atherosclerosis. The complexity of the disease is caused by its multifactorial origin. Besides the traditional risk factors, genetic predisposition is also a strong risk factor. Many studies have intensively researched cardioprotective drugs, which can relieve myocardial ischemia and reperfusion injury, thereby reducing infarct size. A better understanding of abnormal epigenetic pathways in the myocardial pathology may result in new treatment options. Individualized therapy based on genome sequencing is important for an effective future medical treatment. Studies based on multiomics help to better understand the pathophysiological mechanism of several diseases at a molecular level. Epigenomic, transcriptomic, proteomic, and metabolomic research may be essential in detecting the pathological phenotype of myocardial ischemia and ischemic heart failure.

Decades of research and experimental studies have investigated various strategies to prevent acute coronary events. However, significantly efficient preventive methods have not been developed and still remains a challenge to determine if a coronary atherosclerotic plaque will become vulnerable and unstable. This review aims to assess the significance of plaque vulnerability markers, more precisely the role of spotty calcifications in the development of major cardiac events, given that coronary calcification is a hallmark of atherosclerosis. Recent studies have suggested that microcalcifications, spotty calcifications, and the presence of the napkin-ring sign are predictive vulnerable plaque features, and their presence may cause plaque instability.

Inflammation is a key factor in the development of atherosclerosis, a disease characterized by the buildup of plaque in the arteries. COVID-19 infection is known to cause systemic inflammation, but its impact on local plaque vulnerability is unclear. Our study aimed to investigate the impact of COVID-19 infection on coronary artery disease (CAD) in patients who underwent computed tomography angiography (CCTA) for chest pain in the early stages after infection, using an AI-powered solution called CaRi-Heart®. The study included 158 patients (mean age was 61.63 ± 10.14 years) with angina and low to intermediate clinical likelihood of CAD, with 75 having a previous COVID-19 infection and 83 without infection. The results showed that patients who had a previous COVID-19 infection had higher levels of pericoronary inflammation than those who did not have a COVID-19 infection, suggesting that COVID-19 may increase the risk of coronary plaque destabilization. This study highlights the potential long-term impact of COVID-19 on cardiovascular health, and the importance of monitoring and managing cardiovascular risk factors in patients recovering from COVID-19 infection. The AI-powered CaRi-Heart® technology may offer a non-invasive way to detect coronary artery inflammation and plaque instability in patients with COVID-19.