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
Angiology ◽  
1995 ◽  
Vol 46 (7) ◽  
pp. 557-565 ◽  
Author(s):  
Koichi Setsuta ◽  
Yoshihiko Seino ◽  
Yoshifumi Tomita ◽  
Jun Nejima ◽  
Teruo Takano ◽  
...  

Cardiology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Elena V. Grakova ◽  
Sergey N. Shilov ◽  
Kristina V. Kopeva ◽  
Ekaterina N. Berezikova ◽  
Anna A. Popova ◽  
...  

Cardiovascular disease remains the leading cause of mortality accounting up to 40% of all deaths, but, currently, cancer is prominent cause of death globally. Anthracyclines are the cornerstone of chemotherapy in women with breast cancer. However, its clinical use is limited by their cardiotoxic effects that can trigger heart failure development. Vascular toxicity of chemotherapy may be linked with endothelial dysfunction because anthracycline damage of endothelial cells can lead to the development and progression of cardiomyopathy by decreasing the release and activity of endothelial factors and, ultimately, endothelial cell death. These processes suppress anti-inflammatory and vascular reparative functions and initiate the development of future cardiovascular events. Recent studies have shown that chemotherapy may induce toxicity in the vascular endothelium and is accompanied by systemic endothelial dysfunction in patients with diagnosed cardiovascular diseases. Because the initial endothelial cell insult is likely asymptomatic, there is often a long delay between the termination of doxorubicin therapy and the onset of vascular disorders. In this case, genetic susceptibility factor will help to identify susceptible patients in the future. The objectives of this study were to evaluate prognostic role of molecular (endothelin-1) and genetic factors (gene polymorphisms of endothelial nitric oxide (NO) synthase (NOS3, rs1799983), endothelin-1 receptor type A (EDNRA, C+70G, rs5335) and NADPH oxidase (C242T, rs4673) in development of endothelial dysfunction and anthracycline-induced cardiotoxicity in women without cardiovascular diseases.


2016 ◽  
Vol 15 (1) ◽  
pp. 11-26
Author(s):  
Yu. N. Grigorova ◽  
A. Ya. Bagrov ◽  
O. V. Fedorova

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.


1994 ◽  
Vol 64 ◽  
pp. 85
Author(s):  
Ryosuke Yorikane ◽  
Satoshi Sakai ◽  
Takashi Miyauchi ◽  
Takeshi Sakurai ◽  
Yoshitoshi Kasuya ◽  
...  

2016 ◽  
Vol 144 ◽  
pp. 88-102 ◽  
Author(s):  
Stéphanie Hostenbach ◽  
Miguel D’haeseleer ◽  
Ron Kooijman ◽  
Jacques De Keyser

2016 ◽  
Vol 23 (3) ◽  
Author(s):  
Hanna O Palahniuk

Despite overall effort hypertensive disease (HD) is one of the most significant health and social problem. Essential hypertension is believed to be a multifactorial disease and polymorphism of genes that may be responsible for the regulation of blood pressure plays the key role in it. The least explored in this regard is single nucleotide polymorphism of ET-1 leading to the replacement of the amino acids of lysine (Lys) to asparagine (Asn) at position of 198th polypeptide chain (Lys198Asn).The objective of the research was to improve diagnosis of HD severity determining plasma concentration of ET-1, C-type natriuretic peptides (CNP) and the coefficient of CNP/ET-1 in patients with different genotypes of ET-1 gene.Materials and methods. The study involved 79 men without cardiovascular diseases (control group), 62 men with II stage HD and 50 men with HD complicated by chronic heart failure (CHF) II-III classes according to NYHA Classification. All patients were representative by age. Genotyping of ET-1 gene was conducted using polymerase chain reaction. ET-1 concentration in plasma was determined using ELISA method.Results. Lys/Lys genotype of ET-1 gene was found to occur in 65.82% of men in the control group, carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) constituted 34.18%, Lys allele was observed in 79.75% of cases, Asn allele was detected in 20.25% of men. Among patients with II stage HD Lys/Lys genotype of ET-1 gene was observed in 56.45% of cases, the carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) occurred in 43.55% of patients, Lys allele was found in 73.39% of cases, Asn allele was observed in 26.61% of patients. Among men with HD and CHF IIA genotype Lys/Lys was found in 66.00% of cases, carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) was observed in 34.00% of patients, Lys allele was detected in 80.00% of cases, Asn allele was observed in 20.00% of cases. The men from the control group, patients with II stage HD and patients with HD and CHF as the carriers of Asn allele were found to have significantly higher plasma levels of ET-1 (2.53±0.12 fmol/ml, 13.90±0.22 fmol/ml and 14.07±0.18 fmol/ml, respectively) and CNP (2.98±0.08 pmol/ml, 5.90±0.11 pmol/ml and 5.93±0.18 pmol/ml, respectively) in comparison with homozygous carriers of Lys genotype (ET-1constituted 1.41±0.05 fmol/ml, 11.58±0.23 fmol/ml and 0.08±12.89 fmol/ml, respectively, CNP constituted 2.02±0.29 pmol/ml, 4.68±0.12 pmol/ml and 4.88±0.09 pmol/ml, respectively). According to the analysis of the obtained data, coefficient of CNP/ET-1 (0.40±0.003 c.u. and 0.38±0.006 c.u., respectively) and Asn allele (0.42±0.004 c.u. and 0.42±0.007 c.u., respectively) was significantly lower in patients with II stage HD and patients with HD and CHF as the carriers of Lys/Lys genotype in comparison with the control group (1.4±0.04 c.u. and 1.22±0.05 c.u., respectively). Carriers of Asn allele in the control group had significantly lower coefficient of CNP/ET-1 than genotype Lys/Lys carriers. However, the difference in the coefficient of CNP/ET-1 was not observed in patients with HD.Conclusions. Lys/Lys genotype and Lys allele of ET-1 gene were found to dominate among control group and patients with HD of different severity. Plasma concentration of ET-1, CNP were significantly higher and coefficient of CNP/ET-1 was lower in men with II stage HD and HD complicated by CHF than in men without cardiovascular diseases in case of all ET-1 gene genotypes. The carriers of Asn allele of ET-1 gene had significantly higher plasma levels of ET-1 and CNP in each study group.


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