TY - JOUR

T1 - The Notch pathway

T2 - a novel therapeutic target for cardiovascular diseases?

AU - Aquila, Giorgio

AU - Kostina, Aleksandra

AU - Vieceli Dalla Sega, Francesco

AU - Shlyakhto, Eugeniy

AU - Kostareva, Anna

AU - Marracino, Luisa

AU - Ferrari, Roberto

AU - Rizzo, Paola

AU - Malaschicheva, Anna

PY - 2019/8/3

Y1 - 2019/8/3

N2 - 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.

AB - 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.

KW - aortic aneurysm

KW - aortic valve calcification

KW - cardiotoxicity

KW - Dll4

KW - endothelial dysfunction

KW - heart failure

KW - macrophages

KW - Notch

KW - Notch1

KW - ARTERIOVENOUS-MALFORMATIONS

KW - AORTIC-ANEURYSM

KW - HEART-FAILURE

KW - IMPROVES CARDIAC-FUNCTION

KW - ENDOTHELIAL NOTCH1

KW - SIGNALING PATHWAY

KW - CLONAL HEMATOPOIESIS

KW - MYOCARDIAL ISCHEMIA/REPERFUSION

KW - PROMOTES VASCULAR MATURATION

KW - PHASE-I

UR - http://www.scopus.com/inward/record.url?scp=85069529985&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/notch-pathway-novel-therapeutic-target-cardiovascular-diseases

U2 - 10.1080/14728222.2019.1641198

DO - 10.1080/14728222.2019.1641198

M3 - Review article

C2 - 31304807

AN - SCOPUS:85069529985

VL - 23

SP - 695

EP - 710

JO - Expert Opinion on Therapeutic Targets

JF - Expert Opinion on Therapeutic Targets

SN - 1472-8222

IS - 8

ER -