Statins are among the most widely used drug classes in the world. Apart from their basic mechanism of action, which is lowering cholesterol levels, many pleiotropic effects have been described so far, such as anti-inflammatory and antiatherosclerotic effects. A growing number of scientific reports have proven that these drugs have a beneficial effect on the functioning of the nervous system. The first reports proving that lipid-lowering therapy can influence the development of neurological and psychiatric diseases appeared in the 1990s. Despite numerous studies about the mechanisms by which statins may affect the functioning of the central nervous system (CNS), there are still no clear data explaining this effect. Most studies have focused on the metabolic effects of this group of drugs, however authors have also described the pleiotropic effects of statins, pointing to their probable impact on the neurotransmitter system and neuroprotective effects. The aim of this paper was to review the literature describing the impacts of statins on dopamine, serotonin, acetylcholine, and glutamate neurotransmission, as well as their neuroprotective role. This paper focuses on the mechanisms by which statins affect neurotransmission, as well as on their impacts on neurological and psychiatric diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), vascular dementia (VD), stroke, and depression. The pleiotropic effects of statin usage could potentially open floodgates for research in these treatment domains, catching the attention of researchers and clinicians across the globe.

Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces the degradation of the low-density lipoprotein receptor (LDL-R) and, hence, increases the uptake of low-density lipoprotein cholesterol (LDLc) from the bloodstream as well as reducing its concentration. The effectiveness of three monoclonal antibodies, namely, alirocumab (human IgG1/κ monoclonal antibody, genetically engineered in Chinese hamster ovary cells), evolocumab (the first fully human monoclonal antibody), and bococizumab (humanized mouse antibody), in inhibiting the action of PCSK-9 and reducing LDLc levels has been confirmed. The first two, after clinical trials, were approved by the Food and Drug Administration (FDA) and are used primarily in the treatment of autosomal familial hypercholesterolemia and in cases of statin intolerance. They are currently used both as monotherapy and in combination with statins and ezetimibe to intensify therapy and achieve therapeutic goals following the American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines. However, the lipid-lowering effect is not the only effect of action described by researchers that PCSK-9 inhibitors have. This paper is a review of the literature describing the pleiotropic effects of PCSK-9 inhibitors, which belong to a group of drugs that are being increasingly used, especially when standard lipid-lowering therapy fails. The article focuses on activities other than lipid-lowering, such as the anti-atherosclerotic effect and stabilization of atherosclerotic plaque, the anti-aggregation effect, the anticoagulant effect, the antineoplastic effect, and the ability to influence the course of bacterial infections. In this publication, we try to systematically review the current scientific data, both from our own scientific work and knowledge from international publications.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the last discovered member of the family of proprotein convertases (PCs), mainly synthetized in hepatic cells. This serine protease plays a pivotal role in the reduction of the number of low-density lipoprotein receptors (LDLRs) on the surface of hepatocytes, which leads to an increase in the level of cholesterol in the blood. This mechanism and the fact that gain of function (GOF) mutations in PCSK9 are responsible for causing familial hypercholesterolemia whereas loss-of-function (LOF) mutations are associated with hypocholesterolemia, prompted the invention of drugs that block PCSK9 action. The high efficiency of PCSK9 inhibitors (e.g., alirocumab, evolocumab) in decreasing cardiovascular risk, pleiotropic effects of other lipid-lowering drugs (e.g., statins) and the multifunctional character of other proprotein convertases, were the cause for proceeding studies on functions of PCSK9 beyond cholesterol metabolism. In this article, we summarize the current knowledge on the roles that PCSK9 plays in different tissues and perspectives for its clinical use.

Obesity, defined as body mass index (BMI) ≥ 30 kg/m², is one of the most important public health problems. Over one billion people are obese, including 650 million adults, which is 13% of the worldwide population, according to the World Health Organization (WHO). Similar to obesity, mental disorders such as depression and anxiety are huge social problems with serious health implications. There are numerous studies proving a strong link between the prevalence of obesity and depressive disorders, and being overweight is also associated with decreased health-related quality of life (HRQoL). Due to the broad negative impact of obesity on a patient’s health, proper treatment is crucial. Currently, the literature describes many methods of treatment such as dietary treatment, pharmacotherapy using glucagon-like peptide-1 (GLP-1) analogs, orlistat, naltrexone/bupropion (NB), or finally bariatric surgery. The most commonly used methods of obesity treatment significantly improve the patient’s quality of life and reduce the symptoms of depression and anxiety. The aim of our study was to summarize the knowledge about the impact of known and commonly used methods of obesity treatment (e.g., dietary treatment, bariatric surgery, and pharmacological treatment) on mental health and quality of life. For this purpose, we will try to review the current scientific data, originating from international reports.

Atherosclerosis stands out as one of the leading causes of global mortality. The inflammatory response against vascular wall components plays a pivotal role in the atherogenic process. The initiation of this process is notably driven by oxidized low-density lipoprotein (oxLDL) and a range of pro-inflammatory cytokines, with interleukin-1β (Il-1β) and tumor necrosis factor α (TNFα) emerging as particularly significant in the early stages of atherosclerotic plaque formation. In recent years, researchers worldwide have been diligently exploring innovative therapeutic approaches for metabolic diseases, recognizing their impact on the atherogenesis process. Our study aimed to investigate the influence of glucagon-like peptide 1 receptor agonists (GLP-1RA) on cytokine concentrations associated with the initiation of atherosclerotic plaque formation in a group of patients with type 2 diabetes and dyslipidemia. The study encompassed 50 subjects aged 41–81 (mean: 60.7), all diagnosed with type 2 diabetes, dyslipidemia and confirmed atherosclerosis based on B-mode ultrasound. Following a 180-day treatment with dulaglutide or semaglutide, we observed a statistically significant reduction in biochemical markers (oxLDL, TNFα and Il-1β) associated with the initiation of the atherosclerotic process (p < 0.001) within our study group. In addition to the already acknowledged positive effects of GLP-1RA on the metabolic parameters of treated patients, these drugs demonstrated a notable reduction in proinflammatory cytokine concentrations and may constitute an important element of therapy aimed at reducing cardiovascular risk.

Atherosclerosis is a disorder in which, in addition to high cholesterol levels, several plasma factors play a significant role in its development. Among these cytokines and molecules are interleukin 6 (IL-6), interleukin 18 (IL-18), tumor necrosis factor α (TNF-α), metalloproteinase 2 (MMP-2), and metalloproteinase 9 (MMP-9), all of which may contribute to the stabilization of atherosclerotic plaque. The purpose of this study was to determine the effect of advanced lipid-lowering therapy on the levels of these determinants by utilizing proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors in patients with verified high-risk atherosclerotic plaque. Methods: The study involved patients with dyslipidemia who had the presence of unstable atherosclerotic plaque verified by ultrasonography and who were eligible to begin alirocumab treatment. The levels of IL-6, IL, 18, TNF-α, and MMPs were determined in this group before and after three months of therapy. After treatment, a statistically significant decrease in concentrations of Il-18, Il-6, TNF-α (p < 0.001) and MMP-2 (p < 0.05) was observed. Additionally, we observed that the concentrations of these markers were significantly higher in the group of patients prior to initiating therapy than in the control group. Our study’s results suggest that PCSK-9 inhibitor therapy significantly reduces the concentration of factors influencing the stability of atherosclerotic plaque, which may explain their essential importance in reducing cardiovascular risk in patients receiving this treatment.