CBS 2019
CBSMD教育中心
中 文

急性冠脉综合征

Abstract

Recommended Article

Revascularization Strategies in STEMI with Multivessel Disease: Deciding on Culprit Versus Complete-Ad Hoc or Staged Relations between implementation of new treatments and improved outcomes in patients with non-ST-elevation myocardial infarction during the last 20 years: experiences from SWEDEHEART registry 1995 to 2014 Management of Myocardial Revascularization Failure: An Expert Consensus Document of the EAPCI Pharmacotherapy in the Management of Anxiety and Pain During Acute Coronary Syndromes and the Risk of Developing Symptoms of Posttraumatic Stress Disorder Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association Coronary CT Angiography and 5-Year Risk of Myocardial Infarction Epidemiology and Clinical Outcomes of Patients With Inflammatory Bowel Disease Presenting With Acute Coronary Syndrome Phosphoproteomic Analysis of Neonatal Regenerative Myocardium Revealed Important Roles of CHK1 via Activating mTORC1/P70S6K Pathway

Original Research2020 Oct 7;S0022-2828(20)30296-0.

JOURNAL:J Mol Cell Cardio. Article Link

Decreased inspired oxygen stimulates de novo formation of coronary collaterals in adult heart

A Aghajanian, H Zhang, JE Faber et al. Keywords: hypoxia; collateral vessels lessen myocardial ischemia; coronary obstruction; ischemic heart disease; coronary circulation

ABSTRACT

RATIONALE - Collateral vessels lessen myocardial ischemia when acute or chronic coronary obstruction occurs. It has long been assumed that although native (pre-existing) collaterals enlarge in obstructive disease, new collaterals do not form in the adult. However, the latter was recently shown to occur after coronary artery ligation. Understanding the signals that drive this process is challenged by the difficulty in studying collateral vessels directly and the complex milieu of signaling pathways, including cell death, induced by ligation. Herein we show that hypoxemia alone is capable of inducing collateral vessels to form and that the novel gene Rabep2 is required.

 

OBJECTIVE - Hypoxia stimulates angiogenesis during embryonic development and in pathological states. We hypothesized that hypoxia also stimulates collateral formation in adult heart by a process that involves RABEP2, a recently identified protein required for formation of collateral vessels during development.

 

METHODS AND RESULTS - Exposure of mice to reduced FiO 2 induced collateral formation that resulted in smaller infarctions following LAD ligation and that reversed on return to normoxia. Deletion of Rabep2 or knockdown of Vegfa inhibited formation. Hypoxia upregulated Rabep2, Vegfa and Vegfr2 in heart and brain microvascular endothelial cells (HBMVECs). Knockdown of Rabep2 impaired migration of HBMVECs. In contrast to systemic hypoxia, deletion of Rabep2 did not affect collateral formation induced by ischemic injury caused by LAD ligation.

 

CONCLUSIONS - Hypoxia induced formation of coronary collaterals by a process that required VEGFA and RABEP2, proteins also required for collateral formation during development. Knockdown of Rabep2 impaired cell migration, providing one potential mechanism for RABEP2's role in collateral formation. This appears specific to hypoxia, since formation after acute ischemic injury was unaffected in Rabep2 /mice. These findings provide a novel model for studying coronary collateral formation, and demonstrate that hypoxia alone can induce new collaterals to form in adult heart.