scholarly journals Cardiotonic steroids: main effects, therapeutic applications

2016 ◽  
Vol 15 (1) ◽  
pp. 11-26
Author(s):  
Yu. N. Grigorova ◽  
A. Ya. Bagrov ◽  
O. V. Fedorova
Keyword(s):  
Cardiovascular Diseases ◽  
Therapeutic Target ◽  
Vital Role ◽  
Natriuretic Hormone ◽  
Aldosterone Antagonists ◽  
Pathophysiological Role ◽  
Cardiovascular Fibrosis ◽  
Main Effects ◽  
Important Therapeutic Target

For last few decades 'putative natriuretic hormone' have been considered as very important therapeutic target for developing novel therapies for cardiovascular diseases. The present review discusses the pathophysiological role of endogenous cardiotonic steroids with main focus on marinobufagenin (MBG). Recent studies has established that MBG plays a vital role in regulation of electrolyte homeostasis in humans and rodents. Additionally, it has been reported that elevated MBG plasma levels are associated with number of pathological states such as arterial hypertension, chronic kidney disease, preeclampsia and heart failure. It has been demonstrated that MBG-Na/K-ATPase interaction in kidneys regulates renal sodium excretion inducing natriuresis. Further, it has been reported that MBG-Na/K-ATPase interaction in vascular smooth muscle cells could induce vasoconstriction and cardiovascular fibrosis. Thus these facts have established MBG as a potential therapeutic target. Several therapies such as immunoneutralization of MBG with specific monoclonal antibodies and antagonism with aldosterone antagonists have already been proposed. Further studies providing understanding of pathophysiological implications of MBG and signaling pathways could contribute in establishing new therapies for cardiovascular diseases.

scholarly journals Osteopontin in Cardiovascular Diseases

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1047
Author(s):  
Kohsuke Shirakawa ◽  
Motoaki Sano
Keyword(s):  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Therapeutic Target ◽  
Gene Mutations ◽  
Major Adverse Cardiovascular Event ◽  
Matricellular Protein ◽  
Pathological State ◽  
Adverse Cardiovascular Event ◽  
Anti Inflammatory

Unprecedented advances in secondary prevention have greatly improved the prognosis of cardiovascular diseases (CVDs); however, CVDs remain a leading cause of death globally. These findings suggest the need to reconsider cardiovascular risk and optimal medical therapy. Numerous studies have shown that inflammation, pro-thrombotic factors, and gene mutations are focused not only on cardiovascular residual risk but also as the next therapeutic target for CVDs. Furthermore, recent clinical trials, such as the Canakinumab Anti-inflammatory Thrombosis Outcomes Study trial, showed the possibility of anti-inflammatory therapy for patients with CVDs. Osteopontin (OPN) is a matricellular protein that mediates diverse biological functions and is involved in a number of pathological states in CVDs. OPN has a two-faced phenotype that is dependent on the pathological state. Acute increases in OPN have protective roles, including wound healing, neovascularization, and amelioration of vascular calcification. By contrast, chronic increases in OPN predict poor prognosis of a major adverse cardiovascular event independent of conventional cardiovascular risk factors. Thus, OPN can be a therapeutic target for CVDs but is not clinically available. In this review, we discuss the role of OPN in the development of CVDs and its potential as a therapeutic target.

Role of spinal neurons in the maintenance of elevated sympathetic activity: a novel therapeutic target?

2020 ◽  
Vol 319 (3) ◽  
pp. R282-R287
Author(s):  
Maycon I. O. Milanez ◽  
Erika E. Nishi ◽  
Cássia T. Bergamaschi ◽  
Ruy R. Campos
Keyword(s):  
Cardiovascular Diseases ◽  
Therapeutic Target ◽  
Sympathetic Activity ◽  
Spinal Neurons ◽  
Potential Therapeutic Target ◽  
Present Evidence ◽  
Extensive Range ◽  
Vasomotor Activity ◽  
The Brain

The control of sympathetic vasomotor activity involves a complex network within the brain and spinal circuits. An extensive range of studies has indicated that sympathoexcitation is a common feature in several cardiovascular diseases and that strategies to reduce sympathetic vasomotor overactivity in such conditions can be beneficial. In the present mini-review, we present evidence supporting the spinal cord as a potential therapeutic target to mitigate sympathetic vasomotor overactivity in cardiovascular diseases, focusing mainly on the actions of spinal angiotensin II on the control of sympathetic preganglionic neuronal activity.

scholarly journals Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target

2020 ◽  
Vol Volume 13 ◽  
pp. 7411-7422 ◽  
Author(s):  
Lin Tang ◽  
Meng Xu ◽  
Long Zhang ◽  
Lin Qu ◽  
Xiaoyan Liu
Keyword(s):  
Prostate Cancer ◽  
Therapeutic Target ◽  
Cancer Metastasis ◽  
Prostate Cancer Metastasis ◽  
Important Therapeutic Target

scholarly journals Looking for Pyroptosis-Modulating miRNAs as a Therapeutic Target for Improving Myocardium Survival

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Seahyoung Lee ◽  
Eunhyun Choi ◽  
Min-Ji Cha ◽  
Ki-Chul Hwang
Keyword(s):  
Cell Death ◽  
Cardiovascular Diseases ◽  
Inflammatory Response ◽  
Therapeutic Target ◽  
Noncoding Rnas ◽  
Future Studies ◽  
Small Noncoding Rnas ◽  
Regulated Cell Death ◽  
A Current

Pyroptosis is the most recently identified type of regulated cell death with inflammatory response and has characteristics distinct from those of apoptosis or necrosis. Recently, independent studies have reported that small noncoding RNAs termed microRNAs (miRNAs) are involved in the regulation of pyroptosis. Nevertheless, only a handful of empirical data regarding miRNA-dependent regulation of pyroptosis is currently available. This review is aimed to provide a current update on the role of miRNAs in pyroptosis and to offer suggestions for future studies probing miRNAs as a linker connecting pyroptosis to various cardiovascular diseases (CVDs) and their potential as a therapeutic target for preventing excessive cell death of myocardium during CVDs.

Pathophysiological Role of Proteasome-Dependent Proteolytic Pathway in Endothelin-1-Related Cardiovascular Diseases

2003 ◽  
Vol 1 (1) ◽  
pp. 19-26 ◽  
Author(s):  
M. Takaoka ◽  
M. Ohkita ◽  
Y. Matsumura
Keyword(s):  
Cardiovascular Diseases ◽  
Endothelin 1 ◽  
Proteolytic Pathway ◽  
Pathophysiological Role

scholarly journals The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target

2021 ◽  
Vol 22 (4) ◽  
pp. 1693
Author(s):  
Alison Domingues ◽  
Julia Jolibois ◽  
Perrine Marquet de Rougé ◽  
Valérie Nivet-Antoine
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Therapeutic Target ◽  
Redox Status ◽  
Interacting Protein ◽  
Cellular Redox ◽  
Thioredoxin Interacting Protein ◽  
Potential Biomarker ◽  
Ischemic Diseases

Thioredoxin interacting protein (TXNIP) is a metabolism- oxidative- and inflammation-related marker induced in cardiovascular diseases and is believed to represent a possible link between metabolism and cellular redox status. TXNIP is a potential biomarker in cardiovascular and ischemic diseases but also a novel identified target for preventive and curative medicine. The goal of this review is to focus on the novelties concerning TXNIP. After an overview in TXNIP involvement in oxidative stress, inflammation and metabolism, the remainder of this review presents the clues used to define TXNIP as a new marker at the genetic, blood, or ischemic site level in the context of cardiovascular and ischemic diseases.

scholarly journals Ferroptosis Is a Potential Novel Diagnostic and Therapeutic Target for Patients With Cardiomyopathy

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhenyu Zhai ◽  
Pengtao Zou ◽  
Fuxiang Liu ◽  
Zirong Xia ◽  
Juxiang Li
Keyword(s):  
Cell Death ◽  
Cardiovascular Diseases ◽  
Animal Models ◽  
Therapeutic Target ◽  
Myocardial Injury ◽  
Iron Chelators ◽  
Myocardial Cells ◽  
Cell Death Pathway ◽  
Close Relationship

Cardiomyocyte death is a fundamental progress in cardiomyopathy. However, the mechanism of triggering the death of myocardial cells remains unclear. Ferroptosis, which is the nonapoptotic, iron-dependent, and peroxidation-driven programmed cell death pathway, that is abundant and readily accessible, was not discovered until recently with a pharmacological approach. New researches have demonstrated the close relationship between ferroptosis and the development of many cardiovascular diseases, and several ferroptosis inhibitors, iron chelators, and small antioxidant molecules can relieve myocardial injury by blocking the ferroptosis pathways. Notably, ferroptosis is gradually being considered as an important cell death mechanism in the animal models with multiple cardiomyopathies. In this review, we will discuss the mechanism of ferroptosis and the important role of ferroptosis in cardiomyopathy with a special emphasis on the value of ferroptosis as a potential novel diagnostic and therapeutic target for patients suffering from cardiomyopathy in the future.

scholarly journals Effects of (Pro)renin Receptor on Diabetic Cardiomyopathy Pathological Processes in Rats via the PRR-AMPK-YAP Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Xiong ◽  
Xuefei Dong ◽  
Shengnan Li ◽  
Fan Jiang ◽  
Jing Chen ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Diabetic Cardiomyopathy ◽  
Recombinant Adenovirus ◽  
Cardiac Fibroblasts ◽  
Renin Angiotensin System ◽  
Vital Role ◽  
Pathological Process ◽  
Myocardial Inflammation

Diabetic cardiomyopathy (DCM) is a common complication associated with diabetes. The (pro)renin receptor (PRR) is an important member of the local tissue renin-angiotensin system and plays a vital role in many cardiovascular diseases. Yes-associated protein (YAP) also plays a crucial role in many cardiovascular diseases. However, the mechanism responsible for the effects of PRR and YAP on DCM remains unclear. The purpose of this study was to determine the role of PRR in the pathological progression of DCM and whether PRR influences the pathological processes of diabetic cardiomyopathy through YAP. We first established diabetic cardiomyopathy rats model, downregulated the expression of PRR, and upregulated and downregulated the expression of YAP. The levels of myocardial inflammation and fibrosis were then measured and cardiac function was evaluated. In vitro, primary rat cardiac fibroblasts (CFs) were cultured with high glucose, with or without transfection with recombinant adenovirus expressing PRR, and GSK621 was used to observe the effect of AMPK. The levels of inflammation and fibrosis were measured in vitro. The results showed that PRR and YAP silencing alleviated myocardial inflammation and fibrosis. GSK621 blocked the effect of PRR on AMPK and YAP and improved CF inflammation and fibrosis. The inhibition of PRR expression offers a new therapeutic strategy for the treatment of DCM. The effects of PRR on the pathological process of DCM in rats may be mediated via the PRR-AMPK-YAP pathway.

scholarly journals Phosphorylation of NF-κBp65 drives inflammation-mediated hepatocellular carcinogenesis and is a novel therapeutic target

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Xuan Xu ◽  
Yiming Lei ◽  
Lingjun Chen ◽  
Haoxiong Zhou ◽  
Huiling Liu ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Normal Liver ◽  
Vital Role ◽  
Tnf Α ◽  
Hepatocellular Carcinogenesis ◽  
Mtor Signalling ◽  
Novel Therapeutic

Abstract Background Nuclear factor­κB (NF-κB) plays a vital role in hepatocellular carcinoma (HCC). β-arrestin1 (ARRB1) has been proved to enhance the activity of NF-κBp65, and our previous study indicated that ARRB1 promotes hepatocellular carcinogenesis and development of HCC. However, it remains unknown whether p65 is involved in hepatocellular carcinogenesis through the ARRB1-mediated pathway. Methods The levels of NF-κBp65 and NF-κBp65 phosphorylation (p-p65) were assessed in including normal liver, primary HCC and paired paracancerous tissues. Liver-specific p65 knockout mice were used to examine the role of p65 and p-p65 in hepatocarcinogenesis. The mechanism of NF-κBp65 and p-p65 in hepatocarcinogenesis via ARRB1 was also studied both in vitro and in vivo. Results Phosphorylation of NF-κBp65 was markedly upregulated in inflammation-related HCC patients and was significantly increased in mouse hepatic inflammation models, which were induced by tetrachloromethane (CCl4), diethylnitrosamine (DEN), TNF-α, as well as DEN-induced HCC. Hepatocyte-specific p65-deficient mice markedly decreased in the HCC incidence and size of tumours by the repressing of the proliferation of malignant cells in a DEN-induced HCC model. Furthermore, ARRB1 directly bounds p65 to promote the phosphorylation of NF-κBp65 at ser536, resulted in cell malignant proliferation through GSK3β/mTOR signalling. Conclusion The data demonstrated that phosphorylation of NF-κBp65 drives hepatocellular carcinogenesis in response to inflammation-mediated ARRB1, and that inhibition of the phosphorylation of NF-κBp65 restrains the hepatocellular carcinogenesis. The results indicate that phosphorylation of NF-κBp65 is a novel therapeutic target for HCC.

Chemokines: A Potential Therapeutic Target to Suppress Autoimmune Arthritis

2019 ◽  
Vol 25 (27) ◽  
pp. 2937-2946 ◽  
Author(s):  
Mahmood A. Khan ◽  
Nikhil Khurana ◽  
Rafat S. Ahmed ◽  
Sadiq Umar ◽  
Abu H. Md. G. Sarwar ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Cartilage Destruction ◽  
Vital Role ◽  
Future Perspective ◽  
Potential Therapeutic Target ◽  
Mortality And Morbidity ◽  
The Future

Background:: Chemokines are a family of low molecular weight proteins that induce chemotaxis of inflammatory cells, which mainly depends on the recognition of a chemo-attractant gradient and interaction with the substratum. In Rheumatoid Arthritis (RA), abundant chemokines are expressed in synovial tissue, cause inflammatory cells migration into the inflamed joint that necessitates the formation of new blood vessels i.e. angiogenesis. Over the decades, studies showed that continuous inflammation may lead to the loss of tissue architecture and function, causing severe disability and cartilage destruction. In spite of the advancement of modern drug therapy, thousands of arthritic patients suffer mortality and morbidity globally. Thus, there is an urgent need for the development of novel therapeutic agents for the treatment of RA. Methods:: This review is carried out throughout a non-systematic search of the accessible literature, will provide an overview of the current information of chemokine in RA and also exploring the future perspective of the vital role of targeting chemokine in RA treatment. Results:: Since, chemokines are associated with inflammatory cells/leucocyte migration at the site of inflammation in chronic inflammatory diseases and hence, blockade or interference with chemokines activity showing a potential approach for the development of new anti-inflammatory agents. Currently, results obtained from both preclinical and clinical studies showed significant improvement in arthritis. Conclusion:: This review summarizes the role of chemokines and their receptors in the pathogenesis of RA and also indicates possible interactions of chemokines/receptors with various synthetic and natural compounds that may be used as a potential therapeutic target in the future for the treatment of RA.

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