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1.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445477

RESUMO

Mitochondria-derived peptides (MDPs) are small peptides hidden in the mitochondrial DNA, maintaining mitochondrial function and protecting cells under different stresses. Currently, three types of MDPs have been identified: Humanin, MOTS-c and SHLP1-6. MDPs have demonstrated anti-apoptotic and anti-inflammatory activities, reactive oxygen species and oxidative stress-protecting properties both in vitro and in vivo. Recent research suggests that MDPs have a significant cardioprotective role, affecting CVDs (cardiovascular diseases) development and progression. CVDs are the leading cause of death globally; this term combines disorders of the blood vessels and heart. In this review, we focus on the recent progress in understanding the relationships between MDPs and the main cardiovascular risk factors (atherosclerosis, insulin resistance, hyperlipidaemia and ageing). We also will discuss the therapeutic application of MDPs, modified and synthetic MDPs, and their potential as novel biomarkers and therapeutic targets.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Fragmentos de Peptídeos/farmacologia , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Humanos
2.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445084

RESUMO

Atherosclerosis is the major cause of the development of cardiovascular disease, which, in turn, is one of the leading causes of mortality worldwide. From the point of view of pathogenesis, atherosclerosis is an extremely complex disease. A huge variety of processes, such as violation of mitophagy, oxidative stress, damage to the endothelium, and others, are involved in atherogenesis; however, the main components of atherogenesis are considered to be inflammation and alterations of lipid metabolism. In this review, we want to focus on inflammation, and more specifically on the cellular elements of adaptive immunity, T and B cells. It is known that various T cells are widely represented directly in atherosclerotic plaques, while B cells can be found, for example, in the adventitia layer. Of course, such widespread and well-studied cells have attracted attention as potential therapeutic targets for the treatment of atherosclerosis. Various approaches have been developed and tested for their efficacy.


Assuntos
Aterosclerose/imunologia , Linfócitos B/imunologia , Imunidade , Linfócitos T/imunologia , Imunidade Adaptativa , Animais , Aterosclerose/patologia , Linfócitos B/patologia , Humanos , Imunidade Celular , Inflamação/imunologia , Inflamação/patologia , Linfócitos T/patologia
3.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203309

RESUMO

The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid ß-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.


Assuntos
Aterosclerose/metabolismo , Doenças Cardiovasculares/metabolismo , Dislipidemias/metabolismo , Fígado/metabolismo , Animais , Humanos , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia
4.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201756

RESUMO

Diabetes mellitus and related disorders significantly contribute to morbidity and mortality worldwide. Despite the advances in the current therapeutic methods, further development of anti-diabetic therapies is necessary. Mitochondrial dysfunction is known to be implicated in diabetes development. Moreover, specific types of mitochondrial diabetes have been discovered, such as MIDD (maternally inherited diabetes and deafness) and DAD (diabetes and Deafness). Hereditary mitochondrial disorders are caused by certain mutations in the mitochondrial DNA (mtDNA), which encodes for a substantial part of mitochondrial proteins and mitochondrial tRNA necessary for mitochondrial protein synthesis. Study of mtDNA mutations is challenging because the pathogenic phenotype associated with such mutations depends on the level of its heteroplasmy (proportion of mtDNA copies carrying the mutation) and can be tissue-specific. Nevertheless, modern sequencing methods have allowed describing and characterizing a number of mtDNA mutations associated with human disorders, and the list is constantly growing. In this review, we provide a list of mtDNA mutations associated with diabetes and related disorders and discuss the mechanisms of their involvement in the pathology development.


Assuntos
Diabetes Mellitus/genética , Genoma Mitocondrial/genética , Inflamação/genética , Mutação , Animais , Doença Crônica , DNA Mitocondrial/genética , Surdez/genética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Camundongos , Doenças Mitocondriais/genética
5.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946649

RESUMO

COVID-19 is a highly contagious new infection caused by the single-stranded RNA Sars-CoV-2 virus. For the first time, this infection was recorded in December 2019 in the Chinese province of Wuhan. The virus presumably crossed the interspecies barrier and passed to humans from a bat. Initially, the disease was considered exclusively in the context of damage to the respiratory system, but it quickly became clear that the disease also entails serious consequences from various systems, including the cardiovascular system. Among these consequences are myocarditis, myocardial damage, subsequent heart failure, myocardial infarction, and Takotsubo syndrome. On the other hand, clinical data indicate that the presence of chronic diseases in a patient aggravates the course and outcome of coronavirus infection. In this context, the relationship between COVID-19 and atherosclerosis, a condition preceding cardiovascular disease and other disorders of the heart and blood vessels, is particularly interesting. The renin-angiotensin system is essential for the pathogenesis of both coronavirus disease and atherosclerosis. In particular, it has been shown that ACE2, an angiotensin-converting enzyme 2, plays a key role in Sars-CoV-2 infection due to its receptor activity. It is noteworthy that this enzyme is important for the normal functioning of the cardiovascular system. Disruptions in its production and functioning can lead to various disorders, including atherosclerosis.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Aterosclerose/metabolismo , COVID-19/metabolismo , Animais , Aterosclerose/patologia , COVID-19/patologia , Humanos , Sistema Renina-Angiotensina , SARS-CoV-2/fisiologia
6.
Int J Mol Sci ; 22(9)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923295

RESUMO

NAFLD (non-alcoholic fatty liver disease) is a widespread liver disease that is often linked with other life-threatening ailments (metabolic syndrome, insulin resistance, diabetes, cardiovascular disease, atherosclerosis, obesity, and others) and canprogress to more severe forms, such as NASH (non-alcoholic steatohepatitis), cirrhosis, and HCC (hepatocellular carcinoma). In this review, we summarized and analyzed data about single nucleotide polymorphism sites, identified in genes related to NAFLD development and progression. Additionally, the causative role of mitochondrial mutations and mitophagy malfunctions in NAFLD is discussed. The role of mitochondria-related metabolites of the urea cycle as a new non-invasive NAFLD biomarker is discussed. While mitochondria DNA mutations and SNPs (single nucleotide polymorphisms) canbe used as effective diagnostic markers and target for treatments, age and ethnic specificity should be taken into account.


Assuntos
DNA Mitocondrial/genética , Mitocôndrias/genética , Mutação , Hepatopatia Gordurosa não Alcoólica/patologia , Polimorfismo de Nucleotídeo Único , Animais , Progressão da Doença , Humanos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fatores de Risco
7.
Int J Mol Sci ; 22(8)2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33920227

RESUMO

Polycystic ovarian syndrome (PCOS) is the most common endocrine-metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.


Assuntos
DNA Mitocondrial/genética , Inflamação/genética , Mitocôndrias/genética , Síndrome do Ovário Policístico/genética , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/patologia , Mitocôndrias/patologia , Mutação/genética , Estresse Oxidativo/genética , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/patologia
8.
Curr Med Chem ; 22(16): 1903-10, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25876749

RESUMO

Cardiovascular events such as myocardial infarction (MI) and stroke due to enhanced inflammatory atherosclerosis account for increased premature mortality in rheumatoid arthritis (RA). Accumulated evidence suggests that accelerated atherosclerosis and related cardiovascular comorbidities in RA are confounded not only by traditional risk factors (TRF) but also by a number of immune and inflammatory pathways. Since chronic inflammation and autoimmune disorders play a key role in atherosclerosis and related cardiovascular complications in RA, effective suppression of systemic inflammation can be viewed as a strategy for cardiovascular therapy and prevention in this disease. This article overviews some mechanisms of action of methotrexate on TRF, clinical and subclinical manifestations of RA-induced atherosclerosis, and related cardiovascular morbidity and mortality.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Metotrexato/uso terapêutico , Humanos
9.
Curr Pharm Des ; 18(11): 1512-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22364135

RESUMO

Accelerated development of atherosclerosis (AT) in rheumatoid arthritis (RA) stems from common immune-inflammatory mechanisms underlying the diseases. While the key role of activation of the T-cell immune system component is considered to be proved, the role of B-lymphocytes has been investigated insufficiently. Earlier experimental models demonstrated the "atheroprotective" role of B-cells. At the same time, AT development is associated with activation of the B-cell immune system component and manifested by hyperproduction of antibodies to oxidized low density lipoproteins (oxLDL), heat shock proteins, etc. Wide applications of anti-B-cell therapy stimulate active research on effects of B-lymphocytes and their depletion on AT development in RA patients that have a high risk of cardiovascular events (CVE). Experimental models demonstrated that depletion of B2 cells instead of B1 cells under anti-CD20 treatment resulted in a slower development and progression of AT. Research on cardiovascular effects of chimeric antiCD20 monoclonal antibody (rituximab, RTX) in RA is definitely of high interest. Use of RTX in a combination with methotrexate does not increase the risk of serious side effects, including CVE, compared with the sole use of methotrexate. Currently, only few pilot research reports on favorable effects of RTX on the lipid profile and endothelial function in RA patients have been published. According to other authors, the frequency of CVE in RA patients receiving RTX therapy was somewhat higher than that in patients not treated with RTX. In rare cases such side effects as hypotension and arrhythmia were reported under RTX infusion. In addition, investigation of the combined use of statins and RTX is important, since some data are available on a reduced efficacy of RTX when administered with statins. Therefore, further research is required to clarify the role of the B-cell immune system component in AT development and the impact of anti-B cell therapy on the pathogenetic mechanisms of AT and CVE in RA patients.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Linfócitos B/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Biomarcadores , Humanos , Fatores de Risco
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