The peroxisome proliferator-activated receptor (PPAR) family includes three transcription factors: PPARα, PPARβ/δ, and PPARγ. PPAR are nuclear receptors activated by oxidised and nitrated fatty acid derivatives as well as by cyclopentenone prostaglandins (PGA₂ and 15d-PGJ₂) during the inflammatory response. This results in the modulation of the pro-inflammatory response, preventing it from being excessively activated. Other activators of these receptors are nonsteroidal anti-inflammatory drug (NSAID) and fatty acids, especially polyunsaturated fatty acid (PUFA) (arachidonic acid, ALA, EPA, and DHA). The main function of PPAR during the inflammatory reaction is to promote the inactivation of NF-κB. Possible mechanisms of inactivation include direct binding and thus inactivation of p65 NF-κB or ubiquitination leading to proteolytic degradation of p65 NF-κB. PPAR also exert indirect effects on NF-κB. They promote the expression of antioxidant enzymes, such as catalase, superoxide dismutase, or heme oxygenase-1, resulting in a reduction in the concentration of reactive oxygen species (ROS), i.e., secondary transmitters in inflammatory reactions. PPAR also cause an increase in the expression of IκBα, SIRT1, and PTEN, which interferes with the activation and function of NF-κB in inflammatory reactions.

A new group of antidiabetic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT-2 inhibitors), have recently been shown to have anticancer effects and their expression has been confirmed in many cancer cell lines. Given the metabolic reprogramming of these cells in a glucose-based model, the ability of SGLT-2 inhibitors to block the glucose uptake by cancer cells appears to be an attractive therapeutic approach. In addition to tumour cells, SGLT-2s are only found in the proximal tubules in the kidneys. Furthermore, as numerous clinical trials have shown, the use of SGLT-2 inhibitors is well-tolerated and safe in patients with diabetes and/or heart failure. In vitro cell culture studies and preclinical in vivo studies have confirmed that SGLT-2 inhibitors exhibit antiproliferative effects on certain types of cancer. However, the mechanisms of this action remain unclear. Even in those tumour cell types in which SGLT-2 is present, there is sometimes an SGLT-2-independent mechanism of anticancer action of this group of drugs. This article presents the current state of knowledge of the potential mechanisms of the anticancer action of SGLT-2 inhibitors and their possible future application in clinical oncology.

Despite significant advances in the prevention and treatment of heart failure (HF), the prognosis in patients who have been hospitalised on at least one occasion due to exacerbation of HF is still poor. Therefore, a better understanding of the underlying pathophysiological mechanisms of HF is crucial in order to achieve better results in the treatment of this clinical syndrome. One of the areas that, for years, has aroused the interest of researchers is the activation of the immune system and the elevated levels of biomarkers of inflammation in patients with both ischaemic and non-ischaemic HF. Additionally, it is intriguing that the level of circulating pro-inflammatory biomarkers correlates with the severity of the disease and prognosis in this group of patients. Unfortunately, clinical trials aimed at assessing interventions to modulate the inflammatory response in HF have been disappointing, and the modulation of the inflammatory response has had either no effect or even a negative effect on the HF prognosis. The article presents a summary of current knowledge on the role of immune system activation and inflammation in the pathogenesis of HF. Understanding the immunological mechanisms pathogenetically associated with left ventricular remodelling and progression of HF may open up new therapeutic possibilities for HF.

Osteoprotegerin (OPG) is a glycoprotein involved in the regulation of bone remodelling. OPG regulates osteoclast activity by blocking the interaction between the receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL). More and more studies confirm the relationship between OPG and cardiovascular diseases. Numerous studies have confirmed that a high plasma concentration of OPG and a low concentration of tumour necrosis factor–related apoptosis inducing ligand (TRAIL) together with a high OPG/TRAIL ratio are predictors of poor prognosis in patients with myocardial infarction. A high plasma OPG concentration and a high ratio of OPG/TRAIL in the acute myocardial infarction are a prognostic indicator of adverse left ventricular remodelling and of the development of heart failure. Ever more data indicates the participation of OPG in the regulation of the function of vascular endothelial cells and the initiation of the atherosclerotic process in the arteries. Additionally, it has been shown that TRAIL has a protective effect on blood vessels and exerts an anti-atherosclerotic effect. The mechanisms of action of both OPG and TRAIL within the cells of the vascular wall are complex and remain largely unclear. However, these mechanisms of action as well as their interaction in the local vascular environment are of great interest to researchers. This article presents the current state of knowledge on the mechanisms of action of OPG and TRAIL in the circulatory system and their role in cardiovascular diseases. Understanding these mechanisms may allow their use as a therapeutic target in cardiovascular diseases in the future.

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a protein that regulates low-density lipoprotein (LDL) cholesterol metabolism by binding to the hepatic LDL receptor (LDLR), ultimately leading to its lysosomal degradation and an increase in LDL cholesterol (LDLc) levels. Treatment strategies have been developed based on blocking PCSK9 with specific antibodies (alirocumab, evolocumab) and on blocking its production with small regulatory RNA (siRNA) (inclisiran). Clinical trials evaluating these drugs have confirmed their high efficacy in reducing serum LDLc levels and improving the prognosis in patients with atherosclerotic cardiovascular diseases. Most studies have focused on the action of PCSK9 on LDLRs and the subsequent increase in LDLc concentrations. Increasing evidence suggests that the adverse cardiovascular effects of PCSK9, particularly its atherosclerotic effects on the vascular wall, may also result from mechanisms independent of its effects on lipid metabolism. PCSK9 induces the expression of pro-inflammatory cytokines contributing to inflammation within the vascular wall and promotes apoptosis, pyroptosis, and ferroptosis of cardiomyocytes and is thus involved in the development and progression of heart failure. The elimination of PCSK9 may, therefore, not only be a treatment for hypercholesterolaemia but also for atherosclerosis and other cardiovascular diseases. The mechanisms of action of PCSK9 in the cardiovascular system are not yet fully understood. This article reviews the current understanding of the mechanisms of PCSK9 action in the cardiovascular system and its contribution to cardiovascular diseases. Knowledge of these mechanisms may contribute to the wider use of PCSK9 inhibitors in the treatment of cardiovascular diseases.

Myocardial infarction and post-infarction left ventricular remodelling involve a high risk of morbidity and mortality. For this reason, ongoing research is being conducted in order to learn the mechanisms of unfavourable left ventricular remodelling following a myocardial infarction. New biomarkers are also being sought that would allow for early identification of patients with a high risk of post-infarction remodelling and dysfunction of the left ventricle. In recent years, there has been ever more experimental data that confirms the significance of microRNA in cardiovascular diseases. It has been confirmed that microRNAs are stable in systemic circulation, and can be directly measured in patients’ blood. It has been found that significant changes occur in the concentrations of various types of microRNA in myocardial infarction and heart failure patients. Various types of microRNA are also currently being intensively researched in terms of their usefulness as markers of cardiomyocyte necrosis, and predictors of the post-infarction heart failure development. This paper is a summary of the current knowledge on the significance of microRNA in post-infarction left ventricular remodelling and heart failure.