Available online 27 August 2022, 106294

Both “Good CCC” coronary artery disease patients and OGD HUVECs have high PVT1

PVT1 acts via the PVT1-miR-15b-5p-AKT3 axis to activate pro-angiogenic genes

PVT1 knockdown abrogated its pro-angiogenic effects on OGD HUVECs and mouse models

Angiogenesis plays a key role in coronary collateral circulation (CCC), the compensatory formation of new blood vessels during chronic total coronary occlusion. This study aimed to determine whether plasmacytoma variant translocation 1 (PVT1), a long non-coding (lnc) RNA involved in tumor angiogenesis, plays a role in regulating angiogenesis during chronic coronary ischemia.

Patients with coronary artery disease, and ≥90% stenosis, were examined and divided into “Good” and “Poor” CCC groups based on Rentrop Cohen classification. RNA samples were obtained from all patients, as well as from oxygen and glucose-deprived (OGD) HUVECs. PVT1, miR-15b-5p and AKT3 levels were measured with RT-qPCR or Western blot, while HUVEC migration and angiogenesis were detected by, respectively, wound-healing and tube formation assays. Luciferase reporter assay confirmed direct PVT1-miR-15b-5p binding.

Increased PVT1 was found in “Good CCC” patient plasma, along with being highly expressed among OGD HUVECs; PVT1 knockdown reduced HUVEC migration, tube formation, and pro-angiogenic factor expression. Conversely, OGD HUVECs had downregulated miR-15b-5p, and miR-15b-5p overexpression significantly depressed their angiogenic capabilities. These PVT1 knockdown- or miR-15b-5p overexpression-associated reductions in angiogenic effects were reversed by AKT3 overexpression. In vivo, neovascularization and functioning in both ischemic mice hind-limbs and infarcted myocardium injected with ADV-sh-PVT1 were reduced, which were ameliorated by concurrent antagomiR-15b-5p injections.

Circulating PVT1 may serve as a useful biomarker to distinguish between good versus poor CCC, as it is involved in orchestrating angiogenesis via the miR-15b-5p–AKT3 axis; it thus has potential as a target for treating ischemic disease.

coronary collateral circulation

chronic total coronary occlusion

human umbilical vein endothelial cell

left ventricular ejection fraction

long non-coding RNA

metastasis-associated lung adenocarcinoma transcript 1

oxygen and glucose-deprived

plasmacytoma variant translocation 1

long non-coding RNAs

coronary collateral circulation

plasmacytoma variant translocation 1

miR-15b-5p

AKT3

angiogenesis

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