There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.

Small non-coding microRNAs (miRNAs) are implicated in gene regulation, including those involved in coronary artery disease (CAD). Our aim was to identify whether specific serum miRNAs present in the circulating lipoproteins (Lp) are associated with stable or vulnerable CAD patients. A cardiovascular disease-focused screening array was used to assess miRNAs distribution in sera collected from 95 CAD patients: 30 with stable angina (SA), 39 with unstable angina (UA), 26 at one month after myocardial infarction (MI) and 16 healthy control subjects. We found that miR-486, miR-92a and miR-122 presented the highest expression in CAD sera. These miRNA together with miR-125a, miR-146a and miR-33a were further individually analyzed by TaqMan assays. The results were consistent with PCR-array screening data that all of these miRNAs were significantly increased in CAD patients compared to controls. Using a binary logistic regression model, we established that miR-486 and miR-92a in association with some high-density lipoprotein (HDL) components can designate vulnerable CAD patients. Further, all classes of Lp were isolated from sera by density gradient ultracentrifugation. Analysis of the selected miRNAs in each Lp class showed that they were associated mainly with HDL, miR-486 and miR-92a having the highest levels. In UA and MI patients, miR-486 prevailed in HDL₂, while miR-92a prevailed in HDL₃, and their levels discriminate between stable and vulnerable CAD patients. We identified two circulating miRNAs that in association with some lipid metabolism biomarkers can be used as an additional tool to designate vulnerable CAD patients.

Vascular disease was for a long time considered a disease of the old age, but it is becoming increasingly clear that a cumulus of factors can cause early vascular aging (EVA). Inflammation plays a key role in vascular stiffening and also in other pathologies that induce vascular damage. There is a known and confirmed connection between inflammation and atherosclerosis. However, it has taken a long time to prove the beneficial effects of anti-inflammatory drugs on cardiovascular events. Diabetes can be both a product of inflammation and a cofactor implicated in the progression of vascular disease. When diabetes and inflammation are accompanied by obesity, this ominous trifecta leads to an increased incidence of atherothrombotic events. Research into earlier stages of vascular disease, and documentation of vulnerability to premature vascular disease, might be the key to success in preventing clinical events. Modulation of inflammation, combined with strict control of classical cardiovascular risk factors, seems to be the winning recipe. Identification of population subsets with a successful vascular aging (supernormal vascular aging—SUPERNOVA) pattern could also bring forth novel therapeutic interventions.

Perinatal asphyxia (PA) is a burdening pathology with high short-term mortality and severe long-term consequences. Its incidence, reaching as high as 10 cases per 1000 live births in the less developed countries, prompts the need for better awareness and prevention of cases at risk, together with management by easily applicable protocols. PA acts first and foremost on the nervous tissue, but also on the heart, by hypoxia and subsequent ischemia-reperfusion injury. Myocardial development at birth is still incomplete and cannot adequately respond to this aggression. Cardiac dysfunction, including low ventricular output, bradycardia, and pulmonary hypertension, complicates the already compromised circulatory status of the newborn with PA. Multiorgan and especially cardiovascular failure seem to play a crucial role in the secondary phase of hypoxic-ischemic encephalopathy (HIE) and its high mortality rate. Hypothermia is an acceptable solution for HIE, but there is a fragile equilibrium between therapeutic gain and cardiovascular instability. A profound understanding of the underlying mechanisms of the nervous and cardiovascular systems and a close collaboration between the bench and bedside specialists in these domains is compulsory. More resources need to be directed toward the prevention of PA and the consecutive decrease of cardiovascular dysfunction. Not much can be done in case of an unexpected acute event that produces PA, where recognition and prompt delivery are the key factors for a positive clinical result. However, the situation is different for high-risk pregnancies or circumstances that make the fetus more vulnerable to asphyxia. Improving the outcome in these cases is possible through careful monitoring, identifying the high-risk pregnancies, and the implementation of novel prenatal strategies. Also, apart from adequately supporting the heart through the acute episode, there is a need for protocols for long-term cardiovascular follow-up. This will increase our recognition of any lasting myocardial damage and will enhance our perspective on the real impact of PA. The goal of this article is to review data on the cardiovascular consequences of PA, in the context of an immature cardiovascular system, discuss the potential contribution of cardiovascular impairment on short and long-term outcomes, and propose further directions of research in this field.

There is a stringent need to find means for risk stratification of coronary artery diseases (CAD) patients. We aimed at identifying alterations of plasma high-density lipoproteins (HDL) components and their validation as dysfunctional HDL that could discriminate between acute coronary syndrome (ACS) and stable angina (SA) patients. HDL₂ and HDL₃ were isolated from CAD patients’ plasma and healthy subjects. ApolipoproteinAI (apoAI), apoAII, apoCIII, malondialdehyde (MDA), myeloperoxidase (MPO), ceruloplasmin and paraoxonase1 (PON1) were assessed. The anti-inflammatory potential of HDL subfractions was tested by evaluating the secreted inflammatory molecules of tumor necrosis factor α-activated endothelial cells (EC) upon co-incubation with HDL₂ or HDL_3. We found in ACS versus SA patients: 40% increased MPO, MDA, apoCIII in HDL₂ and HDL₃, 35% augmented apoAII in HDL₂, and in HDL₃ increased ceruloplasmin, decreased apoAII (40%) and PON1 protein and activity (15% and 25%). Co-incubation of activated EC with HDL₂ or HDL₃ from CAD patients induced significantly increased levels of secreted inflammatory molecules, 15–20% more for ACS versus SA. In conclusion, the assessed panel of markers correlates with the reduced anti-inflammatory potential of HDL subfractions isolated from ACS and SA patients (mostly for HDL₃ from ACS) and can discriminate between these two groups of CAD patients.

Fetal arrhythmias are mostly benign and transient. However, some of them are associated with structural defects or can cause heart failure, fetal hydrops, and can lead to intrauterine death. The analysis of fetal heart rhythm is based on ultrasound (M-mode and Doppler echocardiography). Irregular rhythm due to atrial ectopic beats is the most common type of fetal arrhythmia and is generally benign. Tachyarrhythmias are diagnosed when the fetal heart rate is persistently above 180 beats per minute (bpm). The most common fetal tachyarrhythmias are paroxysmal supraventricular tachycardia and atrial flutter. Most fetal tachycardias can be terminated or controlled by transplacental or direct administration of anti-arrhythmic drugs. Fetal bradycardia is diagnosed when the fetal heart rate is slower than 110 bpm. Persistent bradycardia outside labor or in the absence of placental pathology is mostly due to atrioventricular (AV) block. Approximately half of fetal heart blocks are in cases with structural heart defects, and AV block in cases with structurally normal heart is often caused by maternal anti-Ro/SSA antibodies. The efficacy of prenatal treatment for fetal AV block is limited. Our review aims to provide a practical guide for the diagnosis and management of common fetal arrythmias, from the joint perspective of the fetal medicine specialist and the cardiologist.