The Notch pathway: a novel therapeutic target for cardiovascular diseases?
Giorgio AquilaAleksandra KostinaFrancesco Vieceli Dalla SegaEugeniy ShlyakhtoAnna KostarevaLuisa MarracinoRoberto FerrariPaola RizzoAnna B MalashichevaPublished in: Expert opinion on therapeutic targets (2019)
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.
Keyphrases
- aortic valve
- heart failure
- cell proliferation
- transcatheter aortic valve replacement
- stem cells
- cardiovascular disease
- aortic aneurysm
- transcatheter aortic valve implantation
- aortic stenosis
- aortic valve replacement
- papillary thyroid
- gene expression
- chronic kidney disease
- cardiovascular events
- nitric oxide
- left ventricular
- cell fate
- coronary artery disease
- palliative care
- risk factors
- cell therapy
- lymph node metastasis
- acute heart failure
- single molecule
- clinical practice