New biomarkers: prospect for diagnosis and monitoring of thyroid disease.

After the metabolic syndrome and its components, thyroid disorders represent the most common endocrine disorders, with increasing prevalence in the last two decades. Thyroid dysfunctions are distinguished by hyperthyroidism, hypothyroidism, or inflammation (thyroiditis) of the thyroid gland, in addition to the presence of thyroid nodules that can be benign or malignant. Thyroid cancer is typically detected via an ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) and cytological examination of the specimen. This approach has significant limitations due to the small sample size and inability to characterize follicular lesions adequately. Due to the rapid advancement of high-throughput molecular biology techniques, it is now possible to identify new biomarkers for thyroid neoplasms that can supplement traditional imaging modalities in postoperative surveillance and aid in the preoperative cytology examination of indeterminate or follicular lesions. Here, we review current knowledge regarding biomarkers that have been reliable in detecting thyroid neoplasms, making them valuable tools for assessing the efficacy of surgical procedures or adjunctive treatment after surgery. We are particularly interested in providing an up-to-date and systematic review of emerging biomarkers, such as mRNA and non-coding RNAs, that can potentially detect thyroid neoplasms in clinical settings. We discuss evidence for miRNA, lncRNA and circRNA dysregulation in several thyroid neoplasms and assess their potential for use as diagnostic and prognostic biomarkers.

Free radicals: Relationship to Human Diseases and Potential Therapeutic applications.

Reactive species are highly-reactive enzymatically, or non-enzymatically produced compounds with important roles in physiological and pathophysiological cellular processes. Although reactive species represent an extensively researched topic in biomedical sciences, many aspects of their roles and functions remain unclear. This review aims to systematically summarize findings regarding the biochemical characteristics of various types of reactive species and specify the localization and mechanisms of their production in cells. In addition, we discuss the specific roles of free radicals in cellular physiology, focusing on the current lines of research that aim to identify the reactive oxygen species-initiated cascades of reactions resulting in adaptive or pathological cellular responses. Finally, we present recent findings regarding the therapeutic modulations of intracellular levels of reactive oxygen species, which may have substantial significance in developing novel agents for treating several diseases.

Tryptophan Metabolism in Atherosclerosis and Diabetes.

The essential amino acid tryptophan (Trp) undergoes catabolism through several pathways, producing biologically active metabolites that significantly impact physiological processes. The metabolic pathway responsible for the majority of Trp catabolism is the kynurenine synthesis pathway (KP). Serotonin and melatonin are among the most essential Trp pathways degradation products. It has emerged that a strong relationship exists between alterations in Trp metabolism and the onset and progression of atherosclerosis and diabetes. Atherosclerosis is a chronic inflammatory disease of the small and medium arteries wall caused by maladaptive local immune responses, which underpins several cardiovascular diseases (CVD). Systemic low-grade immune-mediated inflammation is implicated in atherosclerosis where pro-inflammatory cytokines, such as interferon-γ (IFN-γ), play a significant role. IFN-γ upregulates the enzyme indoleamine 2,3-dioxygenase (IDO), decreasing serum levels of the Trp and increasing metabolite levels of kynurenine. Increased IDO expression and activity could accelerate the atherosclerosis process. Therefore, activated IDO inhibition could offer possible treatment options regarding atherosclerosis management. Diabetes is a chronic metabolic disease characterized by hyperglycemia that, over time, leads to severe damage to the heart, blood vessels, eyes, kidneys, and peripheral nerves. Trp serum levels and lower activity of IDO were higher in future type 2 diabetes (T2DM) patients. This article reviews recent findings on the link between mammalian Trp metabolism and its role in atherosclerosis and diabetes and outlines the intervention strategies.

Alzheimer's and Consciousness: How Much Subjectivity Is Objective?

Does Alzheimer Disease show a decline in cognitive functions that relate to the awareness of external reality? In this paper, we will propose a perspective that patients with increasing symptoms of AD show a change in the awareness of subjective versus objective representative axis of reality thus consequently move to a more internal like perception of reality. This paradigm shift suggests that new insights into the dynamicity of the conscious representation of reality in the AD brain may give us new clues to the very early signs of memory and self-awareness impairment that originates from, in our view the microtubules. Dialog between Adso and William, in Umberto Eco's The Name of the Rose, Third Day: Vespers. "But how does it happen," I said with admiration, "that you were able to solve the mystery of the library looking at it from the outside, and you were unable to solve it when you were inside?" "Thus, God knows the world, because He conceived it in His mind, as if it was from the outside, before it was created, and we do not know its rule, because we live inside it, having found it already made."

Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes.

Cardiovascular disease is the leading global health concern and responsible for more deaths worldwide than any other type of disorder. Atherosclerosis is a chronic inflammatory disease in the arterial wall, which underpins several types of cardiovascular disease. It has emerged that a strong relationship exists between alterations in amino acid (AA) metabolism and the development of atherosclerosis. Recent studies have reported positive correlations between levels of branched-chain amino acids (BCAAs) such as leucine, valine, and isoleucine in plasma and the occurrence of metabolic disturbances. Elevated serum levels of BCAAs indicate a high cardiometabolic risk. Thus, BCAAs may also impact atherosclerosis prevention and offer a novel therapeutic strategy for specific individuals at risk of coronary events. The metabolism of AAs, such as L-arginine, homoarginine, and L-tryptophan, is recognized as a critical regulator of vascular homeostasis. Dietary intake of homoarginine, taurine, and glycine can improve atherosclerosis by endothelium remodeling. Available data also suggest that the regulation of AA metabolism by indoleamine 2,3-dioxygenase (IDO) and arginases 1 and 2 are mediated through various immunological signals and that immunosuppressive AA metabolizing enzymes are promising therapeutic targets against atherosclerosis. Further clinical studies and basic studies that make use of animal models are required. Here we review recent data examining links between AA metabolism and the development of atherosclerosis.

Hyperbaric Oxygen Therapy and Vascular Complications in Diabetes Mellitus.

Vascular complications in patients with diabetes mellitus (DM) are common. Since impaired oxygen balance in plasma plays an important role in the pathogenesis of chronic DM-associated complications, the administration of hyperbaric oxygen therapy (HBOT) has been recommended to influence development of vascular complications. Hyperbaric oxygen therapy involves inhalation of 100% oxygen under elevated pressure from 1.6 to 2.8 absolute atmospheres in hyperbaric chambers. Hyperbaric oxygen therapy increases plasma oxygen solubility, contributing to better oxygen diffusion to distant tissues and preservation of the viability of tissues reversibly damaged by atherosclerosis-induced ischemia, along with microcirculation restoration. Hyperbaric oxygen therapy exerts antiatherogenic, antioxidant, and cardioprotective effects by altering the level and composition of plasma fatty acids and also by promoting signal transduction through membranes, which are impaired by hyperglycemia and hypoxia. In addition, HBOT affects molecules involved in the regulation of nitric oxide synthesis and in that way exerts anti-inflammatory and angiogenic effects in patients with DM. In this review, we explore the recent literature related to the effects of HBOT on DM-related vascular complications.

DES-ROD: Exploring Literature to Develop New Links between RNA Oxidation and Human Diseases.

Normal cellular physiology and biochemical processes require undamaged RNA molecules. However, RNAs are frequently subjected to oxidative damage. Overproduction of reactive oxygen species (ROS) leads to RNA oxidation and disturbs redox (oxidation-reduction reaction) homeostasis. When oxidation damage affects RNA carrying protein-coding information, this may result in the synthesis of aberrant proteins as well as a lower efficiency of translation. Both of these, as well as imbalanced redox homeostasis, may lead to numerous human diseases. The number of studies on the effects of RNA oxidative damage in mammals is increasing by year due to the understanding that this oxidation fundamentally leads to numerous human diseases. To enable researchers in this field to explore information relevant to RNA oxidation and effects on human diseases, we developed DES-ROD, an online knowledgebase that contains processed information from 298,603 relevant documents that consist of PubMed abstracts and PubMed Central full-text articles. The system utilizes concepts/terms from 38 curated thematic dictionaries mapped to the analyzed documents. Researchers can explore enriched concepts, as well as enriched pairs of putatively associated concepts. In this way, one can explore mutual relationships between any combinations of two concepts from used dictionaries. Dictionaries cover a wide range of biomedical topics, such as human genes and proteins, pathways, Gene Ontology categories, mutations, noncoding RNAs, enzymes, toxins, metabolites, and diseases. This makes insights into different facets of the effects of RNA oxidation and the control of this process possible. The usefulness of the DES-ROD system is demonstrated by case studies on some known information, as well as potentially novel information involving RNA oxidation and diseases. DES-ROD is the first knowledgebase based on text and data mining that focused on the exploration of RNA oxidation and human diseases.

Endothelial Dysfunction in Dyslipidaemia: Molecular Mechanisms and Clinical Implications.

The endothelium consists of a monolayer of Endothelial Cells (ECs) which form the inner cellular lining of veins, arteries, capillaries and lymphatic vessels. ECs interact with the blood and lymph. The endothelium fulfils functions such as vasodilatation, regulation of adhesion, infiltration of leukocytes, inhibition of platelet adhesion, vessel remodeling and lipoprotein metabolism. ECs synthesize and release compounds such as Nitric Oxide (NO), metabolites of arachidonic acid, Reactive Oxygen Species (ROS) and enzymes that degrade the extracellular matrix. Endothelial dysfunction represents a phenotype prone to atherogenesis and may be used as a marker of atherosclerotic risk. Such dysfunction includes impaired synthesis and availability of NO and an imbalance in the relative contribution of endothelialderived relaxing factors and contracting factors such as endothelin-1 and angiotensin. This dysfunction appears before the earliest anatomic evidence of atherosclerosis and could be an important initial step in further development of atherosclerosis. Endothelial dysfunction was historically treated with vitamin C supplementation and L-arginine supplementation. Short term improvement of the expression of adhesion molecule and endothelial function during antioxidant therapy has been observed. Statins are used in the treatment of hyperlipidaemia, a risk factor for cardiovascular disease. Future studies should focus on identifying the mechanisms involved in the beneficial effects of statins on the endothelium. This may help develop drugs specifically aimed at endothelial dysfunction.

Effect of Hyperbaric Oxygen Therapy on Fatty Acid Composition and Insulin-like Growth Factor Binding Protein 1 in Adult Type 1 Diabetes Mellitus Patients: A Pilot Study.

OBJECTIVE: Metabolic changes in type 1 diabetes mellitus (T1DM) impair vasodilation, and this leads to tissue hypoxia and microvascular pathology. Hyperbaric oxygen therapy (HBOT) can significantly improve the outcome of ischemic conditions in T1DM patients and reduce vascular complications. The aim of our study was to assess the effects of HBOT on plasma fatty acid (FA) composition, and expression of insulin-like growth factor binding protein 1 (IGFBP-1) in T1DM patients. METHODS: Our study included 24 adult T1DM patients diagnosed with peripheral vascular complications. The patients were exposed to 10 sessions of 100% oxygen inhalation at 2.4 atmosphere absolute for 1 hour. Blood samples were collected at admission and after HBOT for measurement of metabolic parameters, FA composition and IGFBP-1. Measurement of plasma FA composition was determined by gas chromatography. Expression of IGFBP-1 in the serum was estimated by Western blot analysis. RESULTS: HBOT decreased blood levels of total cholesterol (p<0.05), triglycerides (p<0.05) and low-density lipoprotein (p<0.05). HBOT increased plasma levels of individual FAs: palmitic acid (p<0.05), palmitoleic acid (p<0.05), docosapentaenoic acid (p<0.05) and docosahexaenoic acid (p<0.01), and decreased levels of stearic acid (p<0.05), alpha linolenic acid (p<0.05) and linoleic acid (p<0.01). Expression of IGFBP-1 (p<0.01) was increased, whereas the level of insulin (p<0.001) was decreased in the serum after HBOT. CONCLUSIONS: Our results indicate that HBOT exerts beneficial effects in T1DM patients by improving the lipid profile and altering FA composition.

Drug Delivery Systems for Diabetes Treatment.

BACKGROUND: Insulin is essential for the treatment of Type 1 diabetes mellitus (T1DM) and is necessary in numerous cases of Type 2 diabetes mellitus (T2DM). Prolonged administration of anti-diabetic therapy is necessary for the maintenance of the normal glucose levels and thereby preventing vascular complications. A better understanding of the disease per se and the technological progress contribute to the development of new approaches with the aim to achieve better glycemic control. OBJECTIVE: Current therapies for DM are faced with some challenges. The purpose of this review is to analyze in detail the current trends for insulin delivery systems for diabetes treatment. RESULTS: Contemporary ways have been proposed for the management of both types of diabetes by adequate application of drug via subcutaneous, buccal, oral, ocular, nasal, rectal and pulmonary ways. Development of improved oral administration of insulin is beneficial regarding mimicking physiological pathway of insulin and minimizing the discomfort of the patient. Various nanoparticle carriers for oral and other ways of insulin delivery are currently being developed. Engineered specific properties of nanoparticles (NP): controlling toxicity of NP, stability and drug release, can allow delivery of higher concentration of the drug to the desired location. CONCLUSIONS: The successful development of any drug delivery system relies on solving three important issues: toxicity of nanoparticles, stability of nanoparticles, and desired drug release rate at targeted sites. The main goals of future investigations are to improve the existing therapies by pharmacokinetic modifications, development of a fully automatized system to mimic insulin delivery by the pancreas and reduce invasiveness during admission.

Early Effects of Hyperbaric Oxygen on Inducible Nitric Oxide Synthase Activity/Expression in Lymphocytes of Type 1 Diabetes Patients: A Prospective Pilot Study.

This study aimed at examining the early effects of hyperbaric oxygen therapy (HBOT) on inducible nitric oxide synthase (iNOS) activity/expression in lymphocytes of type 1 diabetes mellitus (T1DM) patients. A group of 19 patients (mean age: 63 ± 2.1) with T1DM and with the peripheral arterial disease were included in this study. Patients were exposed to 10 sessions of HBOT in the duration of 1 h to 100% oxygen inhalation at 2.4 ATA. Blood samples were collected for the plasma C-reactive protein (CRP), plasma free fatty acid (FFA), serum nitrite/nitrate, and serum arginase activity measurements. Expression of iNOS and phosphorylation of p65 subunit of nuclear factor-κB (NFκB-p65), extracellular-regulated kinases 1/2 (ERK1/2), and protein kinase B (Akt) were examined in lymphocyte lysates by Western blot. After exposure to HBOT, plasma CRP and FFA were significantly decreased (p < 0.001). Protein expression of iNOS and serum nitrite/nitrate levels were decreased (p < 0.01), while serum arginase activity was increased (p < 0.05) versus before exposure to HBOT. Increased phosphorylation of NFκB-p65 at Ser536 (p < 0.05) and decreased level of NFκB-p65 protein (p < 0.001) in lymphocytes of T1DM patients were observed after HBOT. Decreased phosphorylation of ERK1/2 (p < 0.05) and Akt (p < 0.05) was detected after HBOT. Our results indicate that exposure to HBO decreased iNOS activity/expression via decreasing phosphorylation of ERK1/2 and Akt followed by decreased activity of NFκB.

Homocysteine and Hyperhomocysteinaemia.

Homocysteine (Hcy) is a thiol group containing the amino acid, which naturally occurs in all humans. Hcy is degraded in the body through two metabolic pathways, while a minor part is excreted through kidneys. The chemical reactions that are necessary for degradation of Hcy require the presence of folic acid, vitamins B6 and B12. Consequently, the level of the total Hcy in the serum is influenced by the presence or absence of these vitamins. An elevated level of the Hcy, hyperhomocysteinemia (HHcy) and homocystinuria is connected with occlusive artery disease, especially in the brain, the heart, and the kidney, in addition to venous thrombosis, chronic renal failure, megaloblastic anemia, osteoporosis, depression, Alzheimer's disease, pregnancy problems, and others. Elevated Hcy levels are connected with various pathologies both in adult and child population. Causes of HHcy include genetic mutations and enzyme deficiencies in 5, 10-methylenetetrahydrofolate reductase (MTHFR) methionine synthase (MS), and cystathionine ß-synthase (CßS). HHcy can be caused by deficiencies in the folate, vitamin B12 and to a lesser extent, deficiency in B6 vitamin what influences methionine metabolism. Additionally, HHcy can be caused by the rich diet and renal impairment. This review presents literature data from recent research related to Hcy metabolism and the etiology of the Hcy blood level disorder. In addition, we also described various pathological mechanisms induced by hereditary disturbances or nutritional influences and their association with HHcy induced pathology in adults and children and treatment of these metabolic disorders.

Genetic Markers for Coronary Artery Disease.

Coronary artery disease (CAD) and myocardial infarction (MI) are recognized as leading causes of mortality in developed countries. Although typically associated with behavioral risk factors, such as smoking, sedentary lifestyle, and poor dietary habits, such vascular phenotypes have also long been recognized as being related to genetic background. We review the currently available data concerning genetic markers for CAD in English and non-English articles with English abstracts published between 2003 and 2018. As genetic testing is increasingly available, it may be possible to identify adequate genetic markers representing the risk profile and to use them in a clinical setting.

Interaction of Au(iii) and Pt(ii) complexes with Na/K-ATPase: experimental and theoretical study of reaction stoichiometry and binding sites.

The present paper deals with investigation of the interaction between selected simple structure Au(iii) ([AuCl4]-, [AuCl2(dmso)2]+, [AuCl2(bipy)]+) and Pt(ii) ([PtCl2(dmso)2]) complexes with Na/K-ATPase as the target enzyme, using an experimental and theoretical approach. Reaction stoichiometries and binding constants for these enzyme/complex systems were determined, while kinetic measurements were used in order to reveal the type of inhibition. Based on the results obtained by quantum mechanical calculations (electrostatic surface potential (ESP), volume and surface of the complexes) the nature of the investigated complexes was characterized. By using the solvent accessible surface area (SASA) applied on specific inhibitory sites (ion channel and intracellular domains) the nature of these sites was described. Docking studies were used to determine the theoretical probability of the non-covalent metal binding site positions. Inhibition studies implied that all the investigated complexes decreased the activity of the enzyme while the kinetic analysis indicated an uncompetitive mode of inhibition for the selected complexes. Docking results suggested that the main inhibitory site of all these complexes is located in the ion translocation pathway on the extracellular side in the E2P enzyme conformation, similar to the case of cardiac glycosides, specific Na/K-ATPase inhibitors. Also, based on our knowledge, the hydrolyzed forms of [AuCl4]- and [PtCl2(dmso)2] complexes were investigated for the first time by theoretical calculations in this paper. Thereby, a new inhibitory site situated between the M2 and M4 helices was revealed. Binding in this site induces conformational changes in the enzyme domains and perturbs the E1-E2P conformational equilibrium, causing enzyme inhibition.

PCSK9 and Hypercholesterolemia: Therapeutic Approach.

Despite the intensive research and progress in modern pharmacotherapy, hypercholesterolemia and related cardiovascular complications remain one of the leading causes of mortality and disability in the modern world. A significant contribution to the treatment of hypercholesterolemia was made by the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9). This enzyme is responsible for the degradation of the low-density lipoprotein (LDL) receptor (LDLR) found at the surface of the plasma membrane in the liver and directly associated with serum LDL level. Limitations in standard therapy used in the treatment of lipid disorders have led to the development of new drugs, such as an inhibitor of PCSK9. Over the past years, the greatest achievement in discovering the PCSK9 inhibitor was made by designing monoclonal antibodies that disable PCSK9 to bind LDLR and RNA interference to reduce PCSK9 production, but one of the main disadvantages is costeffectiveness. In this review, we will summarize the most recent findings of basic and clinical studies which focus on PCSK9 function, regulation and therapeutic target for the treatment of hypercholesterolemia and associated cardiovascular diseases.

The influence of oxo-bridged binuclear gold(III) complexes on Na/K-ATPase activity: a joint experimental and theoretical approach.

The in vitro effects of oxo-bridged binuclear gold(III) complexes, i.e., [(bipy2Me)2Au2(µ-O)2][PF6]2 (Auoxo6), Au2[(bipydmb-H)2(µ-O)][PF6] (Au2bipyC) and [Au2(phen2Me)2(µ-O)2](PF6)2 (Au2phen) on Na/K-ATPase, purified from the porcine cerebral cortex, were investigated. All three studied gold complexes inhibited the enzyme activity in a concentration-dependent manner achieving IC50 values in the low micromolar range. Kinetic analysis suggested an uncompetitive mode of inhibition for Auoxo6 and Au2bipyC, and a mixed type one for Au2phen. Docking studies indicated that the inhibitory actions of all tested complexes are related to E2-P enzyme conformation binding to ion channel and intracellular part between N and P sub-domain. In addition, Au2phen was able to inhibit the enzyme by interacting with its extracellular part as well. Toxic effects of the gold(III) complexes were evaluated in vitro by following lactate dehydrogenase activity in rat brain synaptosomes and incidence of micronuclei and cytokinesis-block proliferation index in cultivated human lymphocytes. All investigated complexes turned out to induce cytogenetic damage consisting of a significant decrease in cell proliferation and an increase in micronuclei in a dose-dependent manner. On the other hand, lactate dehydrogenase activity, an indicator of membrane integrity/viability, was not affected by Auoxo6 and Au2bipyC, while Au2phen slightly modified its activity.

Link between Metabolic Syndrome and Insulin Resistance.

Metabolic syndrome (MetS) is a leading public health and clinical challenge worldwide. MetS represents a group of interrelated risk factors that predict cardiovascular diseases (CVD) and diabetes mellitus (DM). Its prevalence ranges between 10 and 84%, depending on the geographic region, urban or rural environment, individual demographic characteristics of the population studied (sex, age, racial and ethnic origin), as well as the criteria used to define MetS. Persons with MetS have higher mortality rate when compared with people without MetS, primarily caused by progressive atherosclerosis, accelerated by pro-inflammatory and pro-coagulation components of MetS. Considering the high prevalence of metabolic disorders (glucose metabolism disorder, hypertension, dyslipidaemia, obesity etc.), preventive healthcare should focus on changing lifestyle in order to reduce obesity and increase physical activity. This narrative review considers the available evidence from clinical and experimental studies dealing with MetS, and current treatment options for patients with insulin resistance and MetS.

Benefits of L-Arginine on Cardiovascular System.

The amino acid, L-Arginine (L-Arg) plays an important role in the cardiovascular system. Data from the literature show that L-Arg is the only substrate for the production of nitric oxide (NO), from which L-Arg develops its effects on the cardiovascular system. As a free radical, NO is synthesized in all mammalian cells by L-Arg with the activity of NO synthase (NOS). In states of hypertension, diabetes, hypercholesterolemia and vascular inflammation a disorder occurs in the metabolic pathway of the synthesis of NO from L-Arg which all together bring alterations of blood vessels. Experimental results obtained on animals, as well as clinical studies show that L-Arg has an effect on thrombocytes, on the process of coagulation and on the fibrolytic system. This mini review represents a summary of the latest scientific animal and human studies related to L-Arg and its mechanisms of actions with a focus on the role of L-Arg via NO pathway in cardiovascular disorders. Moreover, here we present data from recent animal and clinical studies suggesting that L-Arg could be one of the possible therapeutic molecules for improving the treatment of different cardiovascular disorders.

Non-canonical interactions of porphyrins in porphyrin-containing proteins.

In this study we have described the noncanonical interactions between the porphyrin ring and the protein part of porphyrin-containing proteins to better understand their stabilizing role. The analysis reported in this study shows that the predominant type of non-canonical interactions at porphyrins are CH····O and CH····N interactions, with a small percentage of CH···π and noncanonical interactions involving sulfur atoms. The majority of non-canonical interactions are formed from side-chains of charged and polar amino acids, whereas backbone groups are not frequently involved. The main-chain noncanonical interactions might be slightly more linear than the side-chain interactions, and they have somewhat shorter median distances. The analysis, performed in this study, shows that about 44% of the total interactions in the dataset are involved in the formation of multiple (furcated) noncanonical interactions. The high number of porphyrin-water interactions show importance of the inclusion of solvent in protein-ligand interaction studies. Furthermore, in the present study we have observed that stabilization centers are composed predominantly from nonpolar amino acid residues. Amino acids deployed in the environment of porphyrin rings are deposited in helices and coils. The results from this study might be used for structure-based porphyrin protein prediction and as scaffolds for future porphyrin-containing protein design.

Peroxisome proliferator-activated receptors and atherosclerosis.

The peroxisome proliferator-activated receptors (PPARs) represent the family of 3 nuclear receptor isoforms-PPARα, -γ, and -δ/ß, which are encoded by different genes. As lipid sensors, they are primarily involved in regulation of lipid metabolism and subsequently in inflammation and atherosclerosis. Atherosclerosis considers accumulation of the cells and extracellular matrix in the vessel wall leading to the formation of atherosclerotic plaque, atherothrombosis, and other vascular complications. Besides existence of natural ligands for PPARs, their more potent synthetic ligands are fibrates and thiazolidindiones. Future investigations should now focus on the mechanisms of PPARs activation, which might present new approaches involved in the antiatherosclerotic effects revealed in this review. In addition, in this review we are presenting latest data from recent performed clinical studies which have focus on novel approach to PPARs agonists as potential therapeutic agents in the treatment of complex disease such as atherosclerosis.