The Notch pathway: a novel therapeutic target for cardiovascular diseases?

被引:47
作者
Aquila, Giorgio [1 ]
Kostina, Aleksandra [2 ,3 ]
Dalla Sega, Francesco Vieceli [4 ]
Shlyakhto, Eugeniy [2 ]
Kostareva, Anna [2 ]
Marracino, Luisa [5 ,6 ]
Ferrari, Roberto [1 ,4 ]
Rizzo, Paola [4 ,5 ,6 ]
Malaschicheva, Anna [2 ,3 ,7 ]
机构
[1] Univ Ferrara, Dept Med Sci, Ferrara, Italy
[2] Almazov Natl Med Res Ctr, Lab Mol Cardiol, St Petersburg, Russia
[3] Russian Acad Sci, Inst Cytol, Lab Regenerat Biomed, St Petersburg, Russia
[4] Maria Cecilia Hosp, GVM Care & Res, Cotignola, Italy
[5] Univ Ferrara, Dept Morphol Surg & Expt Med, Ferrara, Italy
[6] Univ Ferrara, Lab Technol Adv Therapies LTTA, Ferrara, Italy
[7] St Petersburg State Univ, Fac Biol, Dept Embryol, St Petersburg, Russia
基金
俄罗斯科学基金会;
关键词
Notch; heart failure; aortic aneurysm; aortic valve calcification; endothelial dysfunction; cardiotoxicity; macrophages; Dll4; Notch1; PROMOTES VASCULAR MATURATION; IMPROVES CARDIAC-FUNCTION; SIGNALING PATHWAY; HEART-FAILURE; PHASE-I; MYOCARDIAL ISCHEMIA/REPERFUSION; ARTERIOVENOUS-MALFORMATIONS; CLONAL HEMATOPOIESIS; ENDOTHELIAL NOTCH1; AORTIC-ANEURYSM;
D O I
10.1080/14728222.2019.1641198
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: The Notch pathway is involved in determining cell fate during development and postnatally in continuously renewing tissues, such as the endothelium, the epithelium, and in the stem cells pool. The dysregulation of the Notch pathway is one of the causes of limited response, or resistance, to available cancer treatments and novel therapeutic strategies based on Notch inhibition are being investigated in preclinical and clinical studies in oncology. A large body of evidence now shows that the dysregulation of the Notch pathway is also involved in the pathophysiology of cardiovascular diseases (CVDs).Areas covered: This review discusses the molecular mechanisms involving Notch which underlie heart failure, aortic valve calcification, and aortic aneurysm.Expert opinion: Despite the existence of preventive, pharmacological and surgical interventions approaches, CVDs are the first causes of mortality worldwide. The Notch pathway is becoming increasingly recognized as being involved in heart failure, aortic aneurysm and aortic valve calcification, which are among the most common global causes of mortality due to CVDs. As already shown in cancer, the dissection of the biological processes and molecular mechanisms involving Notch should pave the way for new strategies to prevent and cure these diseases.
引用
收藏
页码:695 / 710
页数:16
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