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Symptom onset-to-balloon time and mortality in the first seven years after STEMI treated with primary percutaneous coronary intervention Cardiac Troponin Elevation in Patients Without a Specific Diagnosis Complete Revascularization with Multivessel PCI for Myocardial Infarction Prognostic Significance of Complex Ventricular Arrhythmias Complicating ST-Segment Elevation Myocardial Infarction From Early Pharmacology to Recent Pharmacology Interventions in Acute Coronary Syndromes Multivessel Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction With Cardiogenic Shock Early Versus Standard Care Invasive Examination and Treatment of Patients with Non-ST-Segment Elevation Acute Coronary Syndrome: The VERDICT (Very EaRly vs Deferred Invasive evaluation using Computerized Tomography) - Randomized Controlled Trial A case of influenza type a myocarditis that presents with ST elevation MI, cardiogenic shock, acute renal failure, and rhabdomyolysis and with rapid recovery after treatment with oseltamivir and intra-aortic balloon pump support Managing Multivessel Coronary Artery Disease in Patients With ST-Elevation Myocardial Infarction: A Comprehensive Review 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction

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.