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2.
Biomater Sci ; 9(18): 6153-6168, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34346410

RESUMO

Foam cells with the pro-inflammatory macrophage phenotype (M1) play an essential role in atherosclerosis progression. Either cellular cholesterol removal or drug intervention was reported to polarize M1 into the anti-inflammatory phenotype (M2) for atherosclerosis regression. These might be realized simultaneously by drug-loaded discoidal reconstituted high-density lipoproteins (d-rHDLs) with the functions of cellular cholesterol efflux and targeted drug delivery on macrophages. However, cholesterol reception can drive the remodelling of d-rHDLs, which serves to release drugs specifically in the atherosclerotic plaque but might incur premature drug leakage in blood circulation. Given that, the proposed strategy is to inhibit the remodelling behaviour of the carrier in blood circulation and responsively accelerate it under the atherosclerotic microenvironmental stimulus. Herein, atorvastatin calcium-loaded d-rHDL was modified by a PEGylated ferrocene/ß-cyclodextrin supramolecular copolymer (PF/TC) to construct ROS-responsive PF/TC-AT-d-rHDL, which is expected to possess plasma stability and biosafety as well as triggered drug release by cholesterol efflux promotion. As a result, PF/TC-AT-d-rHDL could responsively dissemble into ß-cyclodextrin modified AT-d-rHDL under the ROS-triggered dissociation of PF/TC, therefore exhibiting increased cholesterol efflux from the cholesterol donor and drug release through the remodelling behaviour of the carrier in vitro. Moreover, PF/TC-AT-d-rHDL enhanced cellular cholesterol removal in foam cells after response to ROS, inhibiting intracellular lipid deposition compared with other d-rHDL carriers. Interestingly, cellular drug uptake was significantly promoted upon cellular cholesterol removal by restoring the permeability and fluidity of foam cell membranes as indicated by flow cytometry and fluorescence polarization analysis, respectively. Importantly, compared with untreated foam cells, PF/TC-AT-d-rHDL obviously increased the ratio of M2/M1 by 6.3-fold, which was even higher than the effect of PF/TC-d-rHDL (3.4-fold) and free drugs (1.9-fold), revealing that PF/TC-AT-d-rHDL synergistically promoted the M2 polarization of macrophages. Accordingly, PF/TC-AT-d-rHDL boosted the secretion of anti-inflammatory cytokines and inhibited that of inflammatory cytokines. Collectively, PF/TC-AT-d-rHDL exerted synergistic M2 polarization effects on foam cells for atherosclerotic immunomodulatory therapy via responsively mediating cholesterol efflux and delivering drugs.


Assuntos
Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Anti-Inflamatórios , Aterosclerose/tratamento farmacológico , Colesterol , Humanos , Macrófagos
3.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209109

RESUMO

Atherosclerosis is a well-known global health problem. Despite the high prevalence of the disease, numerous aspects of pathogenesis remain unclear. Subsequently, there are still no cure or adequate preventive measures available. Atherogenesis is now considered a complex interplay between lipid metabolism alterations, oxidative stress, and inflammation. Inflammation in atherogenesis involves cellular elements of both innate (such as macrophages and monocytes) and adaptive immunity (such as B-cells and T-cells), as well as various cytokines cascades. Because inflammation is, in general, a well-investigated therapeutic target, and strategies for controlling inflammation have been successfully used to combat a number of other diseases, inflammation seems to be the preferred target for the treatment of atherosclerosis as well. In this review, we summarized data on targeting the most studied inflammatory molecular targets, CRP, IL-1ß, IL-6, IFN-γ, and TNF-α. Studies in animal models have shown the efficacy of anti-inflammatory therapy, while clinical studies revealed the incompetence of existing data, which blocks the development of an effective atheroprotective drug. However, all data on cytokine targeting give evidence that anti-inflammatory therapy can be a part of a complex treatment.


Assuntos
Imunidade Adaptativa , Anti-Inflamatórios/uso terapêutico , Aterosclerose , Citocinas/imunologia , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/imunologia , Aterosclerose/patologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia
4.
Ann Acad Med Singap ; 50(6): 474-480, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34195754

RESUMO

INTRODUCTION: The apolipoprotein E (APOE) gene is a promising candidate for the diagnosis of hyperlipoproteinaemia and atherosclerosis. Polymorphisms in APOE have been reported to result in differential efficacies of statin drugs in atherosclerotic cardiovascular disease. METHODS: We classified the APOE genotypes of 225 patients treated with atorvastatin, and analysed the relation between genotypes and serum lipid levels. RESULTS: The baseline serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly lower in carriers of APOE ε3 than of APOE ε4 genotypes. The serum levels of TC and LDL-C decreased significantly after 1 month of atorvastatin treatment. Atorvastatin has a higher significant effect in reducing serum TC and LDL-C levels in patients with the APOE ε4 genotype. CONCLUSION: Polymorphism in the APOE gene is related to the efficacy of atorvastatin in reducing the serum levels of TC and LDL-C.


Assuntos
Apolipoproteínas E , Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Genótipo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos
6.
Ann Palliat Med ; 10(6): 6793-6803, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34237978

RESUMO

BACKGROUND: It was a meta-analysis on the efficacy of statins in the treatment of atherosclerosis. METHODS: The PubMed, Medline, Embase, Web of Sciences, and other Chinese and English databases were used to retrieve literature on randomized controlled trials (RCTs) of statins in the treatment of atherosclerosis, published from January 2000 to January 2021. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was used to conduct bias risk assessment, and Review Manager 5.3 software (RevMan) was used for meta-analysis. RESULTS: A total of 12 articles with 1,180 participants were included in the meta-analysis. In the observation group, the plaque area [mean difference (MD) =-1.21; 95% confidence interval (CI): -2.03 to -0.38; Z =2.87; P=0.004], total cholesterol (TC) level (MD =-0.72; 95% CI: -1.01 to -0.43; Z =4.83; P<0.00001), triglyceride (TG) level (MD =-0.43; 95% CI: -0.76 to -0.09; Z =2.51; P=0.01), and the low-density lipoprotein (LDL-C) level (MD =-0.79; 95% CI: -1.41 to -0.18; Z =2.54; P=0.01) were lower, while the clinical effective rate (MD =3.64; 95% CI: 1.39 to 9.53; Z =2.64; P=0.008) was higher, and the difference was notable. No notable difference was noted in intra-media thickness (IMT) (MD =-0.41; 95% CI: -0.88 to -0.06; Z =1.7; P=0.09), hypersensitive C-reactive protein (hs-CRP) level (MD =-1.61; 95% CI: -3.59 to 0.37; Z =1.7; P=0.09), and high-density lipoprotein (HDL-C) level (MD =0.14; 95% CI: -0.02 to 0.30; Z =2.54; P=0.09) between the 2 groups. DISCUSSION: The use of statins in the treatment of atherosclerosis can reduce the levels of TC, TG, and LDL-C, mitigate clinical symptoms, and reduce blood lipids with good efficacy.


Assuntos
Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Aterosclerose/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipoproteínas LDL , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Molecules ; 26(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34279384

RESUMO

Curcumin, a natural polyphenolic compound present in Curcuma longa L. rhizomes, shows potent antioxidant, anti-inflammatory, anti-cancer, and anti-atherosclerotic properties. Atherosclerosis is a comprehensive term for a series of degenerative and hyperplasic lesions such as thickening or sclerosis in large- and medium-sized arteries, causing decreased vascular-wall elasticity and lumen diameter. Atherosclerotic cerebro-cardiovascular disease has become a major concern for human health in recent years due to its clinical sequalae of strokes and heart attacks. Curcumin concoction treatment modulates several important signaling pathways related to cellular migration, proliferation, cholesterol homeostasis, inflammation, and gene transcription, among other relevant actions. Here, we provide an overview of curcumin in atherosclerosis prevention and disclose the underlying mechanisms of action of its anti-atherosclerotic effects.


Assuntos
Aterosclerose/tratamento farmacológico , Curcumina/uso terapêutico , Animais , Aterosclerose/metabolismo , Curcumina/farmacologia , Humanos , Transdução de Sinais/efeitos dos fármacos
8.
Int J Mol Sci ; 22(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205487

RESUMO

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with excess mortality worldwide. The cardiovascular system is the second most common target of SARS-CoV-2, which leads to severe complications, including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism, as well as other major thrombotic events because of direct endothelial injury and an excessive systemic inflammatory response. This review focuses on the similarities and the differences of inflammatory pathways involved in COVID-19 and atherosclerosis. Anti-inflammatory agents and immunomodulators have recently been assessed, which may constitute rational treatments for the reduction of cardiovascular events in both COVID-19 and atherosclerotic heart disease.


Assuntos
Aterosclerose/patologia , COVID-19/patologia , Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/virologia , Quimiocinas/metabolismo , Síndrome da Liberação de Citocina/etiologia , Citocinas/metabolismo , Humanos , Prognóstico , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo
9.
Sheng Li Xue Bao ; 73(3): 501-508, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34230951

RESUMO

Atherosclerosis is a chronic inflammatory disease. Cytokine-related research provides an important direction for the prevention and treatment of atherosclerosis. Cytokines, produced by different types of cells and acting on a range of targets, play a key role in the pathogenesis and progression of atherosclerosis. This review summarizes the main pro-inflammatory and anti-inflammatory cytokines related to atherosclerosis and their underlying mechanism. We also outline current anti-atherosclerosis treatments targeting cytokines. The research and treatment prospects of cytokines in the prevention and treatment of atherosclerosis are discussed briefly as well.


Assuntos
Aterosclerose , Citocinas , Anti-Inflamatórios/uso terapêutico , Aterosclerose/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico
10.
Curr Cardiol Rep ; 23(9): 120, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269908

RESUMO

PURPOSE OF REVIEW: Inflammation is involved in the initiation, progression, and destabilization of atherosclerosis. Anti-inflammatory strategies aimed at reducing residual cardiovascular (CV) risk have gained increasing interest in addition to the traditional management of risk factors. Colchicine is a potent anti-inflammatory therapy that affects the inflammasome and other targets. We will herein review the most recent evidence regarding the usefulness of colchicine in patients with coronary artery disease (CAD). RECENT FINDINGS: Colchicine has recently been repurposed from its traditional use to a number of CV indications. The landmark COLCOT and LoDoCo2 trials have demonstrated that long-term use of colchicine was associated with a reduced rate of CV events in both acute and chronic presentations of CAD, with an overall good safety profile. Colchicine is emerging as a valuable, safe, and cost-effective therapy in addition to standard of care for the prevention of atherothrombotic events in CAD.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Infarto do Miocárdio , Anti-Inflamatórios/uso terapêutico , Aterosclerose/tratamento farmacológico , Colchicina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Humanos , Infarto do Miocárdio/tratamento farmacológico
11.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200914

RESUMO

Flavonoids are a group of secondary metabolites derived from plant-based foods, and they offer many health benefits in different stages of several diseases. This review will focus on their effects on ion channels expressed in vascular smooth muscle during atherosclerosis. Since ion channels can be regulated by redox potential, it is expected that during the onset of oxidative stress-related diseases, ion channels present changes in their conductive activity, impacting the progression of the disease. A typical oxidative stress-related condition is atherosclerosis, which involves the dysfunction of vascular smooth muscle. We aim to present the state of the art on how redox potential affects vascular smooth muscle ion channel function and summarize if the benefits observed in this disease by using flavonoids involve restoring the ion channel activity.


Assuntos
Aterosclerose/tratamento farmacológico , Flavonoides/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Animais , Aterosclerose/metabolismo , Progressão da Doença , Humanos , Canais Iônicos/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Oxirredução/efeitos dos fármacos
12.
Kardiologiia ; 61(6): 88-96, 2021 Jul 01.
Artigo em Russo | MEDLINE | ID: mdl-34311692

RESUMO

Along with increased levels of low-density cholesterol, lipid factors of the risk of cardiovascular complications (CVC) include hypertriglyceridemia, particularly increased plasma levels of remnant particles. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are essential for normal functioning of cell membranes, retina, nerve tissue, skeletal muscles, etc. Among the large family of fatty acids (FA), eicosapentaenoic (EPC) and docosahexaenoic (DHX) FA are most studied. The beneficial effect of ω-3 PUFA consumption on the cardiovascular system is related with improvement of blood rheology, antiarrhythmic and anti-inflammatory effects, and a decrease in triglycerides. Large randomized studies of ω-3 PUFA (mixed EPC and DHX or only EPC) have demonstrated their efficiency and safety and a capability for reducing the incidence of CVC and sudden death as well as improvement of the prognosis in various patient populations. In the STRENGTH study (combination of omega-3 and statins), no significant decrease in the risk of CVC was achieved in patients with high triglycerides and low high-density lipoproteins. The ω-3 PUFA treatment is regulated by current international Guidelines and Consensuses as a part of combination therapy with statins for reduction of the risk of CVC and correction of pronounced hypertriglyceridemia.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Ácidos Graxos Ômega-3 , Hipertrigliceridemia , Aterosclerose/tratamento farmacológico , Ácidos Docosa-Hexaenoicos , Humanos , Hipertrigliceridemia/tratamento farmacológico , Triglicerídeos
13.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299240

RESUMO

Glucocorticoids are steroid hormones with key roles in the regulation of many physiological systems including energy homeostasis and immunity. However, chronic glucocorticoid excess, highlighted in Cushing's syndrome, is established as being associated with increased cardiovascular disease (CVD) risk. Atherosclerosis is the major cause of CVD, leading to complications including coronary artery disease, myocardial infarction and heart failure. While the associations between glucocorticoid excess and increased prevalence of these complications are well established, the mechanisms underlying the role of glucocorticoids in development of atheroma are unclear. This review aims to better understand the importance of glucocorticoids in atherosclerosis and to dissect their cell-specific effects on key processes (e.g., contractility, remodelling and lesion development). Clinical and pre-clinical studies have shown both athero-protective and pro-atherogenic responses to glucocorticoids, effects dependent upon their multifactorial actions. Evidence indicates regulation of glucocorticoid bioavailability at the vasculature is complex, with local delivery, pre-receptor metabolism, and receptor expression contributing to responses linked to vascular remodelling and inflammation. Further investigations are required to clarify the mechanisms through which endogenous, local glucocorticoid action and systemic glucocorticoid treatment promote/inhibit atherosclerosis. This will provide greater insights into the potential benefit of glucocorticoid targeted approaches in the treatment of cardiovascular disease.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/fisiopatologia , Glucocorticoides/farmacologia , Aterosclerose/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Síndrome de Cushing , Glucocorticoides/metabolismo , Humanos , Inflamação/tratamento farmacológico , Receptores de Glucocorticoides/metabolismo , Fatores de Risco
14.
J Mater Chem B ; 9(24): 4804-4825, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34085084

RESUMO

Biological stimuli that are present during the pathogenesis of disease have gained considerable interest as a critical element for the design of smart drug delivery systems. Recently, the utilization of biological stimuli-responsive (bioresponsive) nanotheranostic agents to treat atherosclerosis and ischemic-related diseases has demonstrated significant outcomes in preclinical studies. Those diseases share similar hallmarks, including high levels of endogenous reactive oxygen species (ROS), low pH, and high enzyme activity. Interestingly, other relevant biological stimuli such as shear stress, cholesterol, and glutathione have recently been explored as internal stimuli to trigger drug release and some particular actions. In addition, a number of strategies can be proposed to enhance their targeting efficiency, diagnostic properties, and efficacy rate. This review discusses recent advancements in the preclinical studies of bioresponsive nanotherapeutics as diagnostic and therapeutic agents against atherosclerosis and ischemic-related diseases as well as some potential strategies to overcome the current limitations.


Assuntos
Aterosclerose/tratamento farmacológico , Engenharia , Isquemia/tratamento farmacológico , Nanomedicina/métodos , Animais , Humanos
15.
Nutrients ; 13(6)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067469

RESUMO

While targeting elevated serum levels of low-density lipoprotein cholesterol has been the mainstay of atherosclerosis prevention and treatment for decades, the evidence regarding the atherogenic role of hypertriglyceridemia is still controversial. Various epidemiological population-based studies on statin-treated subjects nominated triglycerides, triglyceride-rich lipoproteins (namely, chylomicrons and very-low-density lipoprotein particles), and their remnants as major determinants of the substantial residual cardiovascular risk. With the triglyceride-glucose index and triglyceride to high-density lipoprotein ratio emerging as surrogate indicators of peripheral artery disease and atherosclerotic cerebrovascular disease, one can conclude that further research addressing the intricate relationship between triglycerides and atherosclerosis is warranted. Therefore, this review aims to provide insight into the current clinical and epidemiological state of knowledge on the relationship between triglycerides and atherosclerotic cardiovascular disease. It also intends to highlight the connection between triglycerides and other metabolic disorders, including diabetes mellitus, and the potential benefits of triglyceride-lowering agents on cardiovascular outcomes and all-cause mortality.


Assuntos
Aterosclerose/epidemiologia , Lipoproteínas/sangue , Doenças Metabólicas/epidemiologia , Triglicerídeos/sangue , Adulto , Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Transtornos Cerebrovasculares/epidemiologia , LDL-Colesterol/sangue , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertrigliceridemia/tratamento farmacológico , Hipertrigliceridemia/epidemiologia , Hipolipemiantes/uso terapêutico , Masculino , Doenças Metabólicas/sangue , Pessoa de Meia-Idade , Adulto Jovem
16.
ACS Appl Mater Interfaces ; 13(26): 30930-30940, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34156244

RESUMO

One of the difficulties in atherosclerosis treatment is that the ablation of inflammatory macrophages, repair of vascular endothelial injury, and anti-tissue proliferation should be considered. However, there are few studies that can solve the abovementioned problems simultaneously. Herein, we present a kind of near-infrared (NIR) light-driven multifunctional mesoporous/macroporous tubular micromotor which can rapidly target the damaged blood vessels and release different drugs. Their motion effect can promote themselves to penetrate into the plaque site, and the generated heat effect caused by NIR irradiation can realize the photothermal ablation of inflammatory macrophages. Furthermore, these micromotors can rapidly release the vascular endothelial growth factor for endothelialization and slowly release paclitaxel for antiproliferation to achieve synergistic treatment of atherosclerosis. In vivo results demonstrated that the micromotors can achieve a good therapeutic effect for atherosclerosis. This kind of micro/nanomotor technology with a complex porous structure for drug loading will bring a more potential treatment platform for the disease.


Assuntos
Aterosclerose/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Nanopartículas Metálicas/química , Paclitaxel/uso terapêutico , Dióxido de Silício/química , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Animais , Aorta/patologia , Aterosclerose/patologia , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Ouro/química , Ouro/efeitos da radiação , Células Endoteliais da Veia Umbilical Humana , Humanos , Raios Infravermelhos , Macrófagos/efeitos dos fármacos , Masculino , Nanopartículas Metálicas/efeitos da radiação , Camundongos , Nanotecnologia/métodos , Paclitaxel/química , Terapia Fototérmica , Porosidade , Fator A de Crescimento do Endotélio Vascular/química
18.
Free Radic Biol Med ; 172: 152-166, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34087429

RESUMO

Atherosclerosis develops due to lipid accumulation in the arterial wall and sclerosis as result of increased hyperlipidemia, oxidative stress, lipid oxidation, and protein oxidation. However, improving antioxidant status through diet may prevent the progression of atherosclerotic cardiovascular disease. It is believed that polyphenol-rich plants contribute to the inverse relationship between fruit and vegetable intake and chronic disease. Anthocyanins are flavonoid polyphenols with antioxidant properties that have been associated with reduced risk of cardiovascular disease. The consumption of anthocyanins increases total antioxidant capacity, antioxidant defense enzymes, and HDL antioxidant properties by several measures in preclinical and clinical populations. Anthocyanins appear to impart antioxidant actions via direct antioxidant properties, as well as indirectly via inducing intracellular Nrf2 activation and antioxidant gene expression. These actions counter oxidative stress and inflammatory signaling in cells present in atherosclerotic plaques, including macrophages and endothelial cells. Overall, anthocyanins may protect against atherosclerosis and cardiovascular disease through their effects on cellular antioxidant status, oxidative stress, and inflammation; however, their underlying mechanisms of action appear to be complex and require further elucidation.


Assuntos
Antocianinas , Aterosclerose , Antioxidantes/farmacologia , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Células Endoteliais , Flavonoides , Humanos , Estresse Oxidativo
19.
Curr Opin Lipidol ; 32(4): 231-243, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34116544

RESUMO

PURPOSE OF REVIEW: Coronavirus Disease 2019 (COVID19) has caused significant global morbidity and mortality, especially in persons with underlying cardiovascular disease. There have been concerns that lipid-lowering therapy (LLT) increases angiotensin-converting enzyme 2 levels. Conversely, pleiotropic effects of statins can theoretically protect against severe COVID19 infection, supporting evidence from other respiratory illnesses in which statin use probably confers benefit. RECENT FINDINGS: There is an abundance of studies that show that statins are safe and potentially protect against severe COVID19 infection (critical illness and death), even when adjustment for potential confounders is undertaken. However, the evidence is limited to retrospective cohorts. The benefit for patients with diabetes is less clear. There is a paucity of evidence for other LLT agents. Available clinical guidelines recommend the ongoing use of LLT in patients with COVID19 (unless specifically contra-indicated) and the data from available studies support these. SUMMARY: In patients with COVID19 infection, LLT should be continued. However, the current findings need substantiating in larger prospective clinical studies with specific examination of the possible mechanisms by which LLT confers benefit from COVID19.


Assuntos
Aterosclerose/tratamento farmacológico , COVID-19/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Aterosclerose/complicações , Aterosclerose/epidemiologia , Aterosclerose/virologia , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/virologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/virologia , LDL-Colesterol/efeitos dos fármacos , Dislipidemias/complicações , Dislipidemias/epidemiologia , Dislipidemias/virologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/uso terapêutico , SARS-CoV-2/patogenicidade
20.
Atherosclerosis ; 328: 83-91, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34118596

RESUMO

BACKGROUND AND AIMS: The apolipoprotein A-I mimetic peptide D-4F, among its anti-atherosclerotic effects, improves vasodilation through mechanisms not fully elucidated yet. METHODS: Low-density lipoprotein (LDL) receptor null (LDLr-/-) mice were fed Western diet with or without D-4F. We then measured atherosclerotic lesion formation, endothelial nitric oxide synthase (eNOS) phosphorylation and its association with heat shock protein 90 (HSP90), nitric oxide (NO) and superoxide anion (O2•-) production, and tetrahydrobiopterin (BH4) and GTP-cyclohydrolase 1 (GCH-1) concentration in the aorta. Human umbilical vein endothelial cells (HUVECs) and aortas were treated with oxidized LDL (oxLDL) with or without D-4F; subsequently, BH4 and GCH-1 concentration, NO and O2•- production, eNOS association with HSP90, and endothelium-dependent vasodilation were measured. RESULTS: Unexpectedly, eNOS phosphorylation, eNOS-HSP90 association, and O2•- production were increased, whereas BH4 and GCH-1 concentration and NO production were reduced in atherosclerosis. D-4F significantly inhibited atherosclerosis, eNOS phosphorylation, eNOS-HSP90 association, and O2•- generation but increased NO production and BH4 and GCH-1 concentration. OxLDL reduced NO production and BH4 and GCH-1 concentration but enhanced O2•- generation and eNOS association with HSP90, and impaired endothelium-dependent vasodilation. D-4F inhibited the overall effects of oxLDL. CONCLUSIONS: Hypercholesterolemia enhanced uncoupled eNOS activity by decreasing GCH-1 concentration, thereby reducing BH4 levels. D-4F reduced uncoupled eNOS activity by increasing BH4 levels through GCH-1 expression and decreasing eNOS phosphorylation and eNOS-HSP90 association. Our findings elucidate a novel mechanism by which hypercholesterolemia induces atherosclerosis and D-4F inhibits it, providing a potential therapeutic approach.


Assuntos
Aterosclerose , Óxido Nítrico Sintase Tipo III , Animais , Apolipoproteína A-I , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Biopterina/análogos & derivados , Células Endoteliais , Endotélio Vascular , GTP Cicloidrolase , Guanosina Trifosfato , Camundongos , Óxido Nítrico , Peptídeos , Superóxidos
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