Cholesteryl Ester Transfer Protein (CETP) Variations in Relation to Lipid Profiles and Cardiovascular Diseases: An Update.

Lipid metabolism plays an essential role in the pathogenesis of cardiovascular and metabolic diseases. Cholesteryl ester transfer protein (CETP) is a crucial glycoprotein involved in lipid metabolism by transferring cholesteryl esters (CE) and triglycerides (TG) between plasma lipoproteins. CETP activity results in reduced HDL-C and increased VLDL- and LDL-C concentrations, thus increasing the risk of cardiovascular and metabolic diseases. In this review, we discuss the structure of CETP and its mechanism of action. Furthermore, we focus on recent experiments on animal CETP-expressing models, deciphering the regulation and functions of CETP in various genetic backgrounds and interaction with different external factors. Finally, we discuss recent publications revealing the association of CETP single nucleotide polymorphisms (SNPs) with the risk of cardiovascular and metabolic diseases, lifestyle factors, diet and therapeutic interventions. While CETP SNPs can be used as effective diagnostic markers, diet, lifestyle, gender and ethnic specificity should also be considered for effective treatment.

Role of ABCA1 in Atherosclerosis: Novel Mutations and Potential Plant-derived Therapies.

ATP-binding cassette transporter A1 (ABCA1) is one of the key proteins regulating cholesterol homeostasis and playing a crucial role in atherosclerosis development. ABCA1 regulates the rate-limiting step of reverse cholesterol transport, facilitates the efflux of surplus intracellular cholesterol and phospholipids, and suppresses inflammation through several signalling pathways. At the same time, many mutations and Single Nucleotide Polymorphisms (SNPs) have been identified in the ABCA1 gene, which affects its biological function and is associated with several hereditary diseases (such as familial hypo-alpha-lipoproteinaemia and Tangier disease) and increased risk of cardiovascular diseases (CVDs). This review summarises recently identified mutations and SNPs in their connection to atherosclerosis and associated CVDs. Also, we discuss the recently described application of various plant-derived compounds to modulate ABCA1 expression in different in vitro and in vivo models. Herein, we present a comprehensive overview of the association of ABCA1 mutations and SNPs with CVDs and as a pharmacological target for different natural-derived compounds and highlight the potential application of these phytochemicals for treating atherosclerosis through modulation of ABCA1 expression.

Glycation of LDL: AGEs, impact on lipoprotein function, and involvement in atherosclerosis.

Atherosclerosis is a complex disease, and there are many factors that influence its development and the course of the disease. A deep understanding of the pathological mechanisms underlying atherogenesis is needed to develop optimal therapeutic strategies and treatments. In this review, we have focused on low density lipoproteins. According to multiple studies, their atherogenic properties are associated with multiple modifications of lipid particles. One of these modifications is Glycation. We considered aspects related to the formation of modified particles, as well as the influence of modification on their functioning. We paid special attention to atherogenicity and the role of glycated low-density lipoprotein (LDL) in atherosclerosis.

Modulating mTOR Signaling as a Promising Therapeutic Strategy for Atherosclerosis.

For more than a decade, atherosclerosis has been one of the leading causes of death in developed countries. The issue of treatment and prevention of the disease is especially acute. Despite the huge amount of basic and clinical research, a significant number of gaps remain in our understanding of the pathogenesis of atherosclerosis, and only their closure will bring us closer to understanding the causes of the disease at the cellular and molecular levels and, accordingly, to the development of an effective treatment. One of the seemingly well-studied elements of atherogenesis is the mTOR signaling pathway. However, more and more new details are still being clarified. Therapeutic strategies associated with rapamycin have worked well in a number of different diseases, and there is every reason to believe that targeting components of the mTOR pathway may pay off in atherosclerosis as well.

Role of the mtDNA Mutations and Mitophagy in Inflammaging.

Ageing is an unavoidable multi-factorial process, characterised by a gradual decrease in physiological functionality and increasing vulnerability of the organism to environmental factors and pathogens, ending, eventually, in death. One of the most elaborated ageing theories implies a direct connection between ROS-mediated mtDNA damage and mutations. In this review, we focus on the role of mitochondrial metabolism, mitochondria generated ROS, mitochondrial dynamics and mitophagy in normal ageing and pathological conditions, such as inflammation. Also, a chronic form of inflammation, which could change the long-term status of the immune system in an age-dependent way, is discussed. Finally, the role of inflammaging in the most common neurodegenerative diseases, such as Alzheimer's and Parkinson's, is also discussed.

Heat Shock Protein 90 as Therapeutic Target for CVDs and Heart Ageing.

Cardiovascular diseases (CVDs) are the leading cause of death globally, representing approximately 32% of all deaths worldwide. Molecular chaperones are involved in heart protection against stresses and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins, thus supporting the high metabolic demand of the heart cells. Heat shock protein 90 (HSP90) is one of the main cardioprotective chaperones, represented by cytosolic HSP90a and HSP90b, mitochondrial TRAP1 and ER-localised Grp94 isoforms. Currently, the main way to study the functional role of HSPs is the application of HSP inhibitors, which could have a different way of action. In this review, we discussed the recently investigated role of HSP90 proteins in cardioprotection, atherosclerosis, CVDs development and the involvements of HSP90 clients in the activation of different molecular pathways and signalling mechanisms, related to heart ageing.

The Role of Altered Mitochondrial Metabolism in Thyroid Cancer Development and Mitochondria-Targeted Thyroid Cancer Treatment.

Thyroid cancer (TC) is the most common type of endocrine malignancy. Tumour formation, progression, and metastasis greatly depend on the efficacy of mitochondria-primarily, the regulation of mitochondria-mediated apoptosis, Ca2+ homeostasis, dynamics, energy production, and associated reactive oxygen species generation. Recent studies have successfully confirmed the mitochondrial aetiology of thyroid carcinogenesis. In this review, we focus on the recent progress in understanding the molecular mechanisms of thyroid cancer relating to altered mitochondrial metabolism. We also discuss the repurposing of known drugs and the induction of mitochondria-mediated apoptosis as a new trend in the development of anti-TC therapy.