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Molecular Aspects of Inflammation and Lipid Metabolism in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 July 2023) | Viewed by 25842

Special Issue Editors

Petrovsky National Research Centre of Surgery, 2, Abrikosovsky Lane, 119991 Moscow, Russia
Interests: atherosclerosis; inflammation; macrophages; CRISPR/Cas9; low-density lipoprotein
Special Issues, Collections and Topics in MDPI journals
1. Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, 125315 Moscow, Russia
2. Laboratory of Infection Pathology and Molecular Microecology, Institute of Human Morphology, 3 Tsyurupa Street, 117418 Moscow, Russia
Interests: atherosclerosis; mitophagy; atherogenicity; autoantibodies; inflammation; innate immunity; cell test; macrophage; membrane transport; modified low density lipoprotein; monocyte; transcriptome; trans-sialydase; enzymatic test; cytokine; epigenetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The adequate resolution of inflammation and normal lipid metabolism are vital for maintaining a healthy body state. There is plentiful evidence that disrupted lipid metabolism may cause pro-inflammatory responses in macrophages as well as foam cell formation. In turn, this may lead to the development of atherosclerosis and related cardiovascular diseases. Moreover, it is well-known that chronic inflammation plays an important role in cancer development and the lipid metabolism of metabolic diseases. Thus, this is very important to study these processes, their interaction and their interconnection for the successful diagnosis and treatment of these diseases. In recent years, transcriptomic and bioinformatics analysis have come to the fore as ways to reveal the role of specific genes and signaling pathways in the processes of inflammation and lipid metabolism leading to the development of metabolic diseases. First results of such studies have already demonstrated that both inflammation and lipid metabolism are tightly connected via their molecular pathways. Thus, future meticulous molecular studies of intracellular processes with a bioinformatic approach may give novel insights into the role of inflammation and lipid metabolism in related diseases.

We kindly welcome authors to submit original research papers or reviews to contribute to this Special Issue of International Journal of Molecular Sciences.

Dr. Vasily Nikolaevich Sukhorukov
Prof. Dr. Alexander N. Orekhov
Guest Editors

Manuscript Submission Information

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Keywords

  • inflammation
  • mitochondria
  • cancer
  • atherosclerosis
  • cardiovascular disease
  • lipid metabolism
  • LDL
  • HDL

Published Papers (12 papers)

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Research

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14 pages, 1176 KiB  
Article
Alterations in Plasma Lipid Profiles Associated with Melanoma and Therapy Resistance
by Michele Dei Cas, Chiara Maura Ciniselli, Elisabetta Vergani, Emilio Ciusani, Mariachiara Aloisi, Valeria Duroni, Paolo Verderio, Riccardo Ghidoni, Rita Paroni, Paola Perego, Giovanni Luca Beretta, Laura Gatti and Monica Rodolfo
Int. J. Mol. Sci. 2024, 25(3), 1558; https://doi.org/10.3390/ijms25031558 - 26 Jan 2024
Viewed by 558
Abstract
Dysfunctions of lipid metabolism are associated with tumor progression and treatment resistance of cutaneous melanoma. BRAF/MEK inhibitor resistance is linked to alterations of melanoma lipid pathways. We evaluated whether a specific lipid pattern characterizes plasma from melanoma patients and their response to therapy. [...] Read more.
Dysfunctions of lipid metabolism are associated with tumor progression and treatment resistance of cutaneous melanoma. BRAF/MEK inhibitor resistance is linked to alterations of melanoma lipid pathways. We evaluated whether a specific lipid pattern characterizes plasma from melanoma patients and their response to therapy. Plasma samples from patients and controls were analyzed for FASN and DHCR24 levels and lipidomic profiles. FASN and DHCR24 expression resulted in association with disease condition and related to plasma cholesterol and triglycerides in patients at different disease stages (n = 144) as compared to controls (n = 115). Untargeted lipidomics in plasma (n = 40) from advanced disease patients and controls revealed altered levels of different lipids, including fatty acid derivatives and sphingolipids. Targeted lipidomics identified higher levels of dihydroceramides, ceramides, sphingomyelins, ganglioside GM3, sphingosine, sphingosine-1-phosphate, and dihydrosphingosine, saturated and unsaturated fatty acids. When melanoma patients were stratified based on a long/short-term clinical response to kinase inhibitors, differences in plasma levels were shown for saturated fatty acids (FA 16:0, FA18:0) and oleic acid (FA18:1). Our results associated altered levels of selected lipid species in plasma of melanoma patients with a more favorable prognosis. Although obtained in a small cohort, these results pave the way to lipidomic profiling for melanoma patient stratification. Full article
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19 pages, 5436 KiB  
Article
Atorvastatin Attenuates Diet-Induced Non-Alcoholic Steatohepatitis in APOE*3-Leiden Mice by Reducing Hepatic Inflammation
by José A. Inia, Geurt Stokman, Elsbet J. Pieterman, Martine C. Morrison, Aswin L. Menke, Lars Verschuren, Martien P. M. Caspers, Martin Giera, J. Wouter Jukema, Anita M. van den Hoek and Hans M. G. Princen
Int. J. Mol. Sci. 2023, 24(9), 7818; https://doi.org/10.3390/ijms24097818 - 25 Apr 2023
Cited by 3 | Viewed by 1824
Abstract
Patients with metabolic syndrome are often prescribed statins to prevent the development of cardiovascular disease. Conversely, data on their effects on non-alcoholic steatohepatitis (NASH) are lacking. We evaluated these effects by feeding APOE*3-Leiden mice a Western-type diet (WTD) with or without atorvastatin to [...] Read more.
Patients with metabolic syndrome are often prescribed statins to prevent the development of cardiovascular disease. Conversely, data on their effects on non-alcoholic steatohepatitis (NASH) are lacking. We evaluated these effects by feeding APOE*3-Leiden mice a Western-type diet (WTD) with or without atorvastatin to induce NASH and hepatic fibrosis. Besides the well-known plasma cholesterol lowering (−30%) and anti-atherogenic effects (severe lesion size −48%), atorvastatin significantly reduced hepatic steatosis (−22%), the number of aggregated inflammatory cells in the liver (−80%) and hepatic fibrosis (−92%) compared to WTD-fed mice. Furthermore, atorvastatin-treated mice showed less immunohistochemically stained areas of inflammation markers. Atorvastatin prevented accumulation of free cholesterol in the form of cholesterol crystals (−78%). Cholesterol crystals are potent inducers of the NLRP3 inflammasome pathway and atorvastatin prevented its activation, which resulted in reduced expression of the pro-inflammatory cytokines interleukin (IL)-1β (−61%) and IL-18 (−26%). Transcriptome analysis confirmed strong reducing effects of atorvastatin on inflammatory mediators, including NLRP3, NFκB and TLR4. The present study demonstrates that atorvastatin reduces hepatic steatosis, inflammation and fibrosis and prevents cholesterol crystal formation, thereby precluding NLRP3 inflammasome activation. This may render atorvastatin treatment as an attractive approach to reduce NAFLD and prevent progression into NASH in dyslipidemic patients. Full article
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15 pages, 3404 KiB  
Article
Hepatocyte Nuclear Factor 1α Proinflammatory Effect Linked to the Overexpression of Liver Nuclear Factor–κB in Experimental Model of Chronic Kidney Disease
by Elzbieta Sucajtys-Szulc, Alicja Debska-Slizien, Boleslaw Rutkowski, Marek Szolkiewicz, Julian Swierczynski and Ryszard Tomasz Smolenski
Int. J. Mol. Sci. 2022, 23(16), 8883; https://doi.org/10.3390/ijms23168883 - 10 Aug 2022
Cited by 2 | Viewed by 1329
Abstract
Chronic kidney disease (CKD) is associated with low-grade inflammation that activates nuclear factor–κB (NF–κB), which upregulates the expression of numerous NF–κB responsive genes, including the genes encoding IL-6, ICAM-1, VCAM-1, and MCP-1. Herein, we found the coordinated overexpression of genes encoding RelA/p65 (a [...] Read more.
Chronic kidney disease (CKD) is associated with low-grade inflammation that activates nuclear factor–κB (NF–κB), which upregulates the expression of numerous NF–κB responsive genes, including the genes encoding IL-6, ICAM-1, VCAM-1, and MCP-1. Herein, we found the coordinated overexpression of genes encoding RelA/p65 (a subunit of NF–κB) and HNF1α in the livers of chronic renal failure (CRF) rats—an experimental model of CKD. The coordinated overexpression of RelA/p65 and HNF1α was associated with a significant increase in IL-6, ICAM-1, VCAM-1, and MCP-1 gene expressions. A positive correlation between liver RelA/p65 mRNA levels and a serum concentration of creatinine and BUN suggest that RelA/p65 gene transcription is tightly related to the progression of renal failure. The knockdown of HNF1α in the HepG2 cell line by siRNA led to a decrease in Rel A/p65 mRNA levels. This was associated with a decrease in IL-6, ICAM-1, VCAM-1, and MCP-1 gene expressions. The simultaneous repression of HNF-1α and RelA/p65 by clofibrate is tightly associated with the downregulation of IL-6, ICAM-1, VCAM-1, and MCP-1 gene expression. In conclusion, our findings suggest that NF–κB could be a downstream component of the HNF1α-initiated signaling pathway in the livers of CRF rats. Full article
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12 pages, 4043 KiB  
Article
Effect of Chemically Modified Carbon-Coated Iron Nanoparticles on the Structure of Human Atherosclerotic Plaques Ex Vivo and on Adipose Tissue in Chronic Experiment In Vivo
by Shamil Akhmedov, Sergey Afanasyev, Natalia Beshchasna, Marina Trusova, Ivan Stepanov, Mariya Rebenkova, Ekaterina Poletykina, Yuri Vecherskiy, Sergei Tverdokhlebov, Evgeny Bolbasov, Sascha Balakin, Joerg Opitz, Anatoly Yermakov and Boris Kozlov
Int. J. Mol. Sci. 2022, 23(15), 8241; https://doi.org/10.3390/ijms23158241 - 26 Jul 2022
Cited by 1 | Viewed by 1664
Abstract
The high mortality rate caused by atherosclerosis makes it necessary to constantly search for new and better treatments. In previous reports, chemically modified carbon-coated iron nanoparticles (Fe@C NPs) have been demonstrated a high biocompatibility and promising anti-plaque properties. To further investigate these effects, [...] Read more.
The high mortality rate caused by atherosclerosis makes it necessary to constantly search for new and better treatments. In previous reports, chemically modified carbon-coated iron nanoparticles (Fe@C NPs) have been demonstrated a high biocompatibility and promising anti-plaque properties. To further investigate these effects, the interaction of these nanoparticles with the adipose tissue of Wistar rats (in vivo) and human atherosclerotic plaques (ex vivo) was studied. For the in vivo study, cobalt–chromium (CoCr) alloy tubes, which are used for coronary stent manufacturing, were prepared with a coating of polylactic acid (PLA) which contained either modified or non-modified Fe@C NPs in a 5% by weight concentration. The tubes were implanted into an area of subcutaneous fat in Wistar rats, where changes in the histological structure and functional properties of the surrounding tissue were observed in the case of coatings modified with Fe@C NPs. For the ex vivo study, freshly explanted human atherosclerotic plaques were treated in the physiological solution with doses of modified Fe@C NPs, with mass equal to 5% or 25% relative to the plaques. This treatment resulted in the release of cholesterol-like compounds from the surface of the plaques into the solution, thus proving a pronounced destructive effect on the plaque structure. Chemically modified Fe@C NPs, when used as an anti-atherosclerosis agent, were able to activate the activity of macrophages, which could lead to the destruction of atherosclerotic plaques structures. These findings could prove the fabrication of next-generation vascular stents with built-in anti-atherosclerotic agents. Full article
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Review

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18 pages, 1003 KiB  
Review
Adipocyte- and Monocyte-Mediated Vicious Circle of Inflammation and Obesity (Review of Cellular and Molecular Mechanisms)
by Natalia Todosenko, Olga Khaziakhmatova, Vladimir Malashchenko, Kristina Yurova, Maria Bograya, Maria Beletskaya, Maria Vulf, Larisa Mikhailova, Anastasia Minchenko, Irina Soroko, Igor Khlusov and Larisa Litvinova
Int. J. Mol. Sci. 2023, 24(15), 12259; https://doi.org/10.3390/ijms241512259 - 31 Jul 2023
Cited by 2 | Viewed by 1165
Abstract
Monocytes play a key role in the development of metabolic syndrome, and especially obesity. Given the complex features of their development from progenitor cells, whose regulation is mediated by their interactions with bone marrow adipocytes, the importance of a detailed study of the [...] Read more.
Monocytes play a key role in the development of metabolic syndrome, and especially obesity. Given the complex features of their development from progenitor cells, whose regulation is mediated by their interactions with bone marrow adipocytes, the importance of a detailed study of the heterogeneous composition of monocytes at the molecular and systemic levels becomes clear. Research argues for monocytes as indicators of changes in the body’s metabolism and the possibility of developing therapeutic strategies to combat obesity and components of metabolic syndrome based on manipulations of the monocyte compound of the immune response. An in-depth study of the heterogeneity of bone-marrow-derived monocytes and adipocytes could provide answers to many questions about the pathogenesis of obesity and reveal their therapeutic potential. Full article
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18 pages, 1198 KiB  
Review
Effects of miR-33 Deficiency on Metabolic and Cardiovascular Diseases: Implications for Therapeutic Intervention
by Rebeca Ortega, Bo Liu and Shanta J. Persaud
Int. J. Mol. Sci. 2023, 24(13), 10777; https://doi.org/10.3390/ijms241310777 - 28 Jun 2023
Cited by 3 | Viewed by 1442
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally inhibit gene expression. These small molecules are involved in several biological conditions such as inflammation, cell growth and proliferation, and regulation of energy metabolism. In the context of metabolic and cardiovascular diseases, miR-33 is of [...] Read more.
MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally inhibit gene expression. These small molecules are involved in several biological conditions such as inflammation, cell growth and proliferation, and regulation of energy metabolism. In the context of metabolic and cardiovascular diseases, miR-33 is of particular interest as it has been implicated in the regulation of lipid and glucose metabolism. This miRNA is located in introns harboured in the genes encoding sterol regulatory element-binding protein (SREBP)-1 and SREBP-2, which are key transcription factors involved in lipid biosynthesis and cholesterol efflux. This review outlines the role of miR-33 in a range of metabolic and cardiovascular pathologies, such as dyslipidaemia, nonalcoholic fatty liver disease (NAFLD), obesity, diabetes, atherosclerosis, and abdominal aortic aneurysm (AAA), and it provides discussion about the effectiveness of miR-33 deficiency as a possible therapeutic strategy to prevent the development of these diseases. Full article
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19 pages, 2435 KiB  
Review
Meta-Inflammation and New Anti-Diabetic Drugs: A New Chance to Knock Down Residual Cardiovascular Risk
by Alessia d’Aiello, Alice Bonanni, Ramona Vinci, Daniela Pedicino, Anna Severino, Antonio De Vita, Simone Filomia, Mattia Brecciaroli and Giovanna Liuzzo
Int. J. Mol. Sci. 2023, 24(10), 8643; https://doi.org/10.3390/ijms24108643 - 12 May 2023
Cited by 2 | Viewed by 1842
Abstract
Type 2 diabetes mellitus (DM) represents, with its macro and microvascular complications, one of the most critical healthcare issues for the next decades. Remarkably, in the context of regulatory approval trials, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 [...] Read more.
Type 2 diabetes mellitus (DM) represents, with its macro and microvascular complications, one of the most critical healthcare issues for the next decades. Remarkably, in the context of regulatory approval trials, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) proved a reduced incidence of major adverse cardiovascular events (MACEs), i.e., cardiovascular death and heart failure (HF) hospitalizations. The cardioprotective abilities of these new anti-diabetic drugs seem to run beyond mere glycemic control, and a growing body of evidence disclosed a wide range of pleiotropic effects. The connection between diabetes and meta-inflammation seems to be the key to understanding how to knock down residual cardiovascular risk, especially in this high-risk population. The aim of this review is to explore the link between meta-inflammation and diabetes, the role of newer glucose-lowering medications in this field, and the possible connection with their unexpected cardiovascular benefits. Full article
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24 pages, 1410 KiB  
Review
The Role of Cytokines in Cholesterol Accumulation in Cells and Atherosclerosis Progression
by Alexander M. Markin, Yuliya V. Markina, Anastasia I. Bogatyreva, Taisiya V. Tolstik, Deyyara A. Chakal, Denis G. Breshenkov and Eduard R. Charchyan
Int. J. Mol. Sci. 2023, 24(7), 6426; https://doi.org/10.3390/ijms24076426 - 29 Mar 2023
Cited by 5 | Viewed by 1791
Abstract
Atherosclerosis is the most common cardiovascular disease and is the number one cause of death worldwide. Today, atherosclerosis is a multifactorial chronic inflammatory disease with an autoimmune component, accompanied by the accumulation of cholesterol in the vessel wall and the formation of atherosclerotic [...] Read more.
Atherosclerosis is the most common cardiovascular disease and is the number one cause of death worldwide. Today, atherosclerosis is a multifactorial chronic inflammatory disease with an autoimmune component, accompanied by the accumulation of cholesterol in the vessel wall and the formation of atherosclerotic plaques, endothelial dysfunction, and chronic inflammation. In the process of accumulation of atherogenic lipids, cells of the immune system, such as monocytes, macrophages, dendritic cells, etc., play an important role, producing and/or activating the production of various cytokines—interferons, interleukins, chemokines. In this review, we have tried to summarize the most important cytokines involved in the processes of atherogenesis. Full article
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22 pages, 2857 KiB  
Review
miRNA Molecules—Late Breaking Treatment for Inflammatory Bowel Diseases?
by Ioanna Aggeletopoulou, Athanasia Mouzaki, Konstantinos Thomopoulos and Christos Triantos
Int. J. Mol. Sci. 2023, 24(3), 2233; https://doi.org/10.3390/ijms24032233 - 23 Jan 2023
Cited by 2 | Viewed by 1594
Abstract
MicroRNAs (miRNAs) are a group of non-coding RNAs that play a critical role in regulating epigenetic mechanisms in inflammation-related diseases. Inflammatory bowel diseases (IBDs), which primarily include ulcerative colitis (UC) and Crohn’s disease (CD), are characterized by chronic recurrent inflammation of intestinal tissues. [...] Read more.
MicroRNAs (miRNAs) are a group of non-coding RNAs that play a critical role in regulating epigenetic mechanisms in inflammation-related diseases. Inflammatory bowel diseases (IBDs), which primarily include ulcerative colitis (UC) and Crohn’s disease (CD), are characterized by chronic recurrent inflammation of intestinal tissues. Due to the multifactorial etiology of these diseases, the development of innovative treatment strategies that can effectively maintain remission and alleviate disease symptoms is a major challenge. In recent years, evidence for the regulatory role of miRNAs in the pathogenetic mechanisms of various diseases, including IBD, has been accumulating. In light of these findings, miRNAs represent potential innovative candidates for therapeutic application in IBD. In this review, we discuss recent findings on the role of miRNAs in regulating inflammatory responses, maintaining intestinal barrier integrity, and developing fibrosis in clinical and experimental IBD. The focus is on the existing literature, indicating potential therapeutic application of miRNAs in both preclinical experimental IBD models and translational data in the context of clinical IBD. To date, a large and diverse data set, which is growing rapidly, supports the potential use of miRNA-based therapies in clinical practice, although many questions remain unanswered. Full article
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19 pages, 950 KiB  
Review
The Role of Inflammation and Oxidative Stress in Rheumatic Heart Disease
by Beata Franczyk, Anna Gluba-Brzózka, Magdalena Rysz-Górzyńska and Jacek Rysz
Int. J. Mol. Sci. 2022, 23(24), 15812; https://doi.org/10.3390/ijms232415812 - 13 Dec 2022
Cited by 1 | Viewed by 3963
Abstract
Rheumatic heart disease (RHD), an acquired valvular disease, remains an important cause of morbidity and mortality in developing countries. This chronic illness starts from untreated streptococcal throat infection, resulting in acute rheumatic fever (ARF) in susceptible individuals. Repeated infections lead to a chronic [...] Read more.
Rheumatic heart disease (RHD), an acquired valvular disease, remains an important cause of morbidity and mortality in developing countries. This chronic illness starts from untreated streptococcal throat infection, resulting in acute rheumatic fever (ARF) in susceptible individuals. Repeated infections lead to a chronic phase characterized by the damage of heart valves. Inflammation has been found to play important role in the development of this disease. All the studies presented in this review clearly show the involvement of the inflammatory state in the progression of this disease. However, the exact role of cytokines in inflammation sites remains to be examined, since most studies have so far focused on peripheral blood. Such analysis would provide information on inflammatory mechanisms in situ. Full article
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17 pages, 685 KiB  
Review
The Role of Adipokines in Inflammatory Mechanisms of Obesity
by Tatiana V. Kirichenko, Yuliya V. Markina, Anastasia I. Bogatyreva, Taisiya V. Tolstik, Yurgita R. Varaeva and Antonina V. Starodubova
Int. J. Mol. Sci. 2022, 23(23), 14982; https://doi.org/10.3390/ijms232314982 - 29 Nov 2022
Cited by 21 | Viewed by 4969
Abstract
Adipokines are currently widely studied cellular signaling proteins produced by adipose tissue and involved in various processes, including inflammation; energy and appetite modulation; lipid and glucose metabolism; insulin sensitivity; endothelial cell functioning; angiogenesis; the regulation of blood pressure; and hemostasis. The current review [...] Read more.
Adipokines are currently widely studied cellular signaling proteins produced by adipose tissue and involved in various processes, including inflammation; energy and appetite modulation; lipid and glucose metabolism; insulin sensitivity; endothelial cell functioning; angiogenesis; the regulation of blood pressure; and hemostasis. The current review attempted to highlight the key functions of adipokines in the inflammatory mechanisms of obesity, its complications, and its associated diseases. An extensive search for materials on the role of adipokines in the pathogenesis of obesity was conducted online using the PubMed and Scopus databases until October 2022. Full article
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13 pages, 509 KiB  
Review
Aging of Vascular System Is a Complex Process: The Cornerstone Mechanisms
by Anastasia V. Poznyak, Nikolay K. Sadykhov, Andrey G. Kartuesov, Evgeny E. Borisov, Vasily N. Sukhorukov and Alexander N. Orekhov
Int. J. Mol. Sci. 2022, 23(13), 6926; https://doi.org/10.3390/ijms23136926 - 22 Jun 2022
Cited by 1 | Viewed by 2402
Abstract
Aging is one of the most intriguing processes of human ontogenesis. It is associated with the development of a wide variety of diseases affecting all organs and their systems. The victory over aging is the most desired goal of scientists; however, it is [...] Read more.
Aging is one of the most intriguing processes of human ontogenesis. It is associated with the development of a wide variety of diseases affecting all organs and their systems. The victory over aging is the most desired goal of scientists; however, it is hardly achievable in the foreseeable future due to the complexity and ambiguity of the process itself. All body systems age, lose their performance, and structural disorders accumulate. The cardiovascular system is no exception. And it is cardiovascular diseases that occupy a leading position as a cause of death, especially among the elderly. The aging of the cardiovascular system is well described from a mechanical point of view. Moreover, it is known that at the cellular level, a huge number of mechanisms are involved in this process, from mitochondrial dysfunction to inflammation. It is on these mechanisms, as well as the potential for taking control of the aging of the cardiovascular system, that we focused on in this review. Full article
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