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Abstract: FR-PO344

MicroRNAs May Predict End-Organ Damage in Severe Hypertension: An Experimental Animal Model

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Langlo, Knut Asbjørn Rise, Norwegian University of Science and Technology, Trondheim, Norway
  • Silva, Gustavo Jose Justo, Norwegian University of Science and Technology, Trondheim, Norway
  • Overrein, Tina Syvertsen, St. Olavs Hospital, Trondheim, Norway
  • Wisloff, Ulrik, Norwegian University of Science and Technology, Trondheim, Norway
  • Rolim, Natale, NTNU, Trondheim, Norway
  • Hallan, Stein I., Norwegian University of Science and Technology, Trondheim, Norway
Background

Severe hypertension is a potentially life-threatening condition if complicated by vital organ failure. The clinical challenge is to differentiate patients in risk of these serious complications from those with solely severely elevated blood pressure. Therefore, we aimed to investigate how hypertension-induced end-organ damage altered the level of circulating microRNAs (miRs) in an experimental model of severe hypertension.

Methods

Dahl salt-sensitive rats were randomized in low-salt (LS, N=20: 0.3% NaCl) or high-salt (HS, N=60: 8% NaCl) diet. Mean systolic blood pressure was 152 mmHg (SD 18,2) in the LS group and 205 mmHg (SD 19,9) in the HS group (p<0,001). Hypertensive encephalopathy (HE) and thrombotic microangiopathy (TMA) were accessed by histology, heart failure with preserved ejection fraction (HFpEF) by echocardiography and endothelial dysfunction (ED) by acetylcholine-induced relaxation.

Results

Partial least squares discriminant analysis (PLS-DA) analysis (VIP-score cut-off at 1.2) predicted 28 miRs for ED, 29 miRs for HE, 30 miRs for HFpEF, and 24 miRs for TMA. ROC curve further identified the miRs that better separate disease from non-disease animals: miR-28-5p for ED (AUC=0.778), miR-151-5p for HE (AUC=0.779), let7c-5p for HFpEF (AUC=0.897), and miR-21-5p for TMA (AUC=0.971). Additionally, we have identified a common signature of circulating miRs using (PLS-DA VIP-score above 1,0) for all 4 outcomes (let-7b-5p, miR-21-5p, miR-484, let-7a-5p, miR-130b-3p, let-7e-5p, and miR-342-3p). Interestingly, KEGG analysis revealed an enrichment of pathways related to TGF-beta signaling (p=3.58E-08), adherens junction (p=6.62E-08), HIF-1 signaling (p=4.43E-04), p53 signaling (p=3,280E-03), and ECM-receptor interaction (p=8.11E-03).

Conclusion

This shows that miRs may serve as biomarkers to identify serious end-organ failure in severe hypertension. Analysis also show that different hypertension induced end-organ failures may be caused by common pathways.

Funding

  • Government Support - Non-U.S.