Mitochondria-Targeted Antioxidants as a Therapeutic Strategy for Protecting Endothelium in Cardiovascular Diseases

2014 ◽  
Vol 21 (25) ◽  
pp. 2989-3006 ◽  
Author(s):  
Nadezda Apostolova ◽  
Milagros Rocha ◽  
Susana Rovira-Llopis ◽  
Celia Banuls ◽  
Rosa Falcon ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Therapeutic Strategy

scholarly journals Modulating endothelial nitric oxide synthase: a new cardiovascular therapeutic strategy

2011 ◽  
Vol 301 (3) ◽  
pp. H634-H646 ◽  
Author(s):  
Yixuan Zhang ◽  
Stefan P. Janssens ◽  
Kirstin Wingler ◽  
Harald H. H. W. Schmidt ◽  
An L. Moens
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Diseases ◽  
Endothelial Nitric Oxide Synthase ◽  
Therapeutic Strategy ◽  
No Synthase ◽  
Superoxide Formation ◽  
No Signaling ◽  
No Bioavailability ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

The pathogenesis of many cardiovascular diseases is associated with reduced nitric oxide (NO) bioavailability and/or increased endothelial NO synthase (eNOS)-dependent superoxide formation. These findings support that restoring and conserving adequate NO signaling in the heart and blood vessels is a promising therapeutic intervention. In particular, modulating eNOS, e.g., through increasing the bioavailability of its substrate and cofactors, enhancing its transcription, and interfering with other modulators of eNOS pathway, such as netrin-1, has a high potential for effective treatments of cardiovascular diseases. This review provides an overview of the possibilities for modulating eNOS and how this may be translated to the clinic in addition to describing the genetic models used to study eNOS modulation.

scholarly journals Killing Two Birds with One Stone by Administration of Soluble ACE2: A Promising Strategy to Treat Both Cardiovascular Diseases and SARS-CoV-2 Infection

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2243
Author(s):  
Fengling Feng ◽  
Jiaoshan Chen ◽  
Jin Zhao ◽  
Yanjun Li ◽  
Minchao Li ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Therapeutic Strategy ◽  
Therapeutic Agent ◽  
Cardiovascular Complications ◽  
Therapeutic Agents ◽  
Cell Entry ◽  
Host Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
High Affinity ◽  
Promising Strategy

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells mainly by the angiotensin converting enzyme 2 (ACE2) receptor, which can recognize the spike (S) protein by its extracellular domain. Previously, recombinant soluble ACE2 (sACE2) has been clinically used as a therapeutic treatment for cardiovascular diseases. Recent data demonstrated that sACE2 can also be exploited as a decoy to effectively inhibit the cell entry of SARS-CoV-2, through blocking SARS-CoV-2 binding to membrane-anchored ACE2. In this study, we summarized the current findings on the optimized sACE2-based strategies as a therapeutic agent, including Fc fusion to prolong the half-life of sACE2, deep mutagenesis to create high-affinity decoys for SARS-CoV-2, or designing the truncated functional fragments to enhance its safety, among others. Considering that COVID-19 patients are often accompanied by manifestations of cardiovascular complications, we think that administration of sACE2 in COVID-19 patients may be a promising therapeutic strategy to simultaneously treat both cardiovascular diseases and SARS-CoV-2 infection. This review would provide insights for the development of novel therapeutic agents against the COVID-19 pandemic.

scholarly journals The Role of Epoxyeicosatrienoic Acids in Cardiac Remodeling

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinsheng Lai ◽  
Chen Chen
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Diseases ◽  
Cardiac Remodeling ◽  
Therapeutic Strategy ◽  
Myocardial Hypertrophy ◽  
Epoxyeicosatrienoic Acids ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Related Drug

Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by cytochrome P450 (CYP) epoxygenases, which include four regioisomers: 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET. Each of them possesses beneficial effects against inflammation, fibrosis, and apoptosis, which could combat cardiovascular diseases. Numerous studies have demonstrated that elevation of EETs by overexpression of CYP2J2, inhibition of sEH, or treatment with EET analogs showed protective effects in various cardiovascular diseases, including hypertension, myocardial infarction, and heart failure. As is known to all, cardiac remodeling is the major pathogenesis of cardiovascular diseases. This review will begin with the introduction of EETs and their protective effects in cardiovascular diseases. In the following, the roles of EETs in cardiac remodeling, with a particular emphasis on myocardial hypertrophy, apoptosis, fibrosis, inflammation, and angiogenesis, will be summarized. Finally, it is suggested that upregulation of EETs is a potential therapeutic strategy for cardiovascular diseases. The EET-related drug development against cardiac remodeling is also discussed, including the overexpression of CYP2J2, inhibition of sEH, and the analogs of EET.

Differentiation of Adipose Tissue-Derived Stem Cells into Cardiomyocytes: An Overview

2022 ◽  
Vol 12 (2) ◽  
pp. 427-431
Author(s):  
Wenju Yan ◽  
Yan Li ◽  
Gaiqin Li ◽  
Luhua Yin ◽  
Huanyi Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Adipose Tissue ◽  
Smooth Muscle ◽  
Cardiovascular Diseases ◽  
Therapeutic Strategy ◽  
Healthcare Systems ◽  
Separation Procedure ◽  
Effective Therapeutic Strategy

Cardiovascular diseases, including congenital and acquired cardiovascular diseases, impose a severe burden on healthcare systems worldwide. Although bone marrow-derived stem cells (BMSCs) therapy can be an effective therapeutic strategy for the heart disease, relatively low abundance, difficult accessibility, and small tissue volume hinder the clinical usefulness. Adipose tissue-derived stem cells (ADSCs) show similar potential with BMSCs to differentiate into lineages and tissues, such as smooth muscle cells, endothelial cells, and adipocytes, with attractiveness of obtaining adipose tissue easily and repeatedly, and a simple separation procedure. We briefly summarize the current understanding of the cardiomyocytes differentiated from ADSCs

scholarly journals Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy

2020 ◽  
Author(s):  
Bo Jin ◽  
Haiming Shi ◽  
Zhu Jun ◽  
Bangwei Wu ◽  
Quzhen Geshang
Keyword(s):  
Animal Model ◽  
Cardiovascular Diseases ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Therapeutic Strategy ◽  
Volume Fraction ◽  
Pathological Process ◽  
Cardiac Myosin ◽  
Pathological Mechanism

Abstract Background: Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM). Methods: We explored whether up-regulating autophagy could improve cardiac function in mice with experimental DCM through the mTOR-4EBP1 pathway. Animal model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Both up- or down-regulation of autophagy were studied by administration of rapamycin or 3-MA in parallel. Morphology, Western blotting, and echocardiography were applied to confirm the pathological mechanisms. Results: Autophagy was activated and autophagosomes were significantly increased in the rapamycin group. The collagen volume fraction (CVF) was decreased in the rapamycin group compared with the DCM group (9.21 ± 0.82 % vs 14.38 ± 1.24 %, P<0.01). The expression of p-mTOR and p-4EBP1 were significantly decreased in rapamycin-induced autophagy activation, while the levels were increased by down-regulating autophagy with 3-MA. In the rapamycin group, the LVEF and FS were significantly increased compared with the DCM group (54.12 ± 6.48 % vs 45.29 ± 6.68 %, P <0.01; 26.89 ± 4.04 % vs 22.17 ± 2.82 %, P <0.05). As the inhibitor of autophagy, 3-MA aggravated the progress of maladaptive cardiac remodeling and declined cardiac function in DCM mice. Conclusions: The study indicated a possible mechanism for improving cardiac function in mice with experimental DCM by up-regulating autophagy via the mTOR-4EBP1 pathway, which could be a promising therapeutic strategy for DCM.

scholarly journals Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy

2019 ◽  
Author(s):  
Bo Jin ◽  
Haiming Shi ◽  
Zhu Jun ◽  
Bangwei Wu ◽  
Quzhen Geshang
Keyword(s):  
Animal Model ◽  
Cardiovascular Diseases ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Therapeutic Strategy ◽  
Volume Fraction ◽  
Pathological Process ◽  
Cardiac Myosin ◽  
Pathological Mechanism

Abstract Background: Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM).Methods: We explored whether up-regulating autophagy could improve cardiac function in mice with experimental DCM through the mTOR-4EBP1 pathway. Animal model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Both up- or down-regulation of autophagy were studied by administration of rapamycin or 3-MA in parallel. Morphology, Western blotting, and echocardiography were applied to confirm the pathological mechanisms.Results: Autophagy was activated and autophagosomes were significantly increased in the rapamycin group. The collagen volume fraction (CVF) was decreased in the rapamycin group compared with the DCM group (9.21 ± 0.82 % vs 14.38 ± 1.24 %, P<0.01). The expression of p-mTOR and p-4EBP1 were significantly decreased in rapamycin-induced autophagy activation, while the levels were increased by down-regulating autophagy with 3-MA. In the rapamycin group, the LVEF and FS were significantly increased compared with the DCM group (54.12 ± 6.48 % vs 45.29 ± 6.68 %, P<0.01; 26.89 ± 4.04 % vs 22.17 ± 2.82 %, P<0.05). As the inhibitor of autophagy, 3-MA aggravated the progress of maladaptive cardiac remodeling and declined cardiac function in DCM mice.Conclusions: The study indicated a possible mechanism for improving cardiac function in mice with experimental DCM by up-regulating autophagy via the mTOR-4EBP1 pathway, which could be a promising therapeutic strategy for DCM.

scholarly journals Probiotics as Beneficial Dietary Supplements to Prevent and Treat Cardiovascular Diseases: Uncovering Their Impact on Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Elisardo C. Vasquez ◽  
Thiago M. C. Pereira ◽  
Veronica A. Peotta ◽  
Marcelo P. Baldo ◽  
Manuel Campos-Toimil
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Gut Microbiota ◽  
Therapeutic Strategy ◽  
Distal Part ◽  
Dietary Intervention ◽  
Cardiovascular Effects ◽  
Beneficial Effects ◽  
Patients With Heart Failure ◽  
Symbiotic Community

The gut microbiota, the ecosystem formed by a wide symbiotic community of nonpathogenic microorganisms that are present in the distal part of the human gut, plays a prominent role in the normal physiology of the organism. The gut microbiota’s imbalance, gut dysbiosis, is directly related to the origin of various processes of acute or chronic dysfunction in the host. Therefore, the ability to intervene in the gut microbiota is now emerging as a possible tactic for therapeutic intervention in various diseases. From this perspective, evidence is growing that a functional dietary intervention with probiotics, which maintain or restore beneficial bacteria of the digestive tract, represents a promising therapeutic strategy for interventions in cardiovascular diseases and also reduces the risk of their occurrence. In the present work, we review the importance of maintaining the balance of the intestinal microbiota to prevent or combat such processes as arterial hypertension or endothelial dysfunction, which underlie many cardiovascular disorders. We also review how the consumption of probiotics can improve autonomic control of cardiovascular function and provide beneficial effects in patients with heart failure. Among the known effects of probiotics is their ability to decrease the generation of reactive oxygen species and, therefore, reduce oxidative stress. Therefore, in this review, we specifically focus on this antioxidant capacity and its relationship with the beneficial cardiovascular effects described for probiotics.

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