Long non-coding RNAs H19 and NKILA are associated with the risk of death and lacunar stroke in the elderly population

Tetiana Lapikova-Bryhinska; Stefano Ministrini; Yustina M Puspitasari; Simon Kraler; Shafeeq Ahmed Mohamed; Sarah Costantino; Francesco Paneni; Michael Khetsuriani; Susan Bengs; Luca Liberale; Fabrizio Montecucco; Wolfgang Krampla; Peter Riederer; Margareta Hinterberger; Peter Fischer; Thomas F Lüscher; Edna Grünblatt; Alexander Akhmedov; Giovanni G Camici

doi:10.1016/j.ejim.2023.11.013

Long non-coding RNAs H19 and NKILA are associated with the risk of death and lacunar stroke in the elderly population

Eur J Intern Med. 2023 Nov 17:S0953-6205(23)00411-9. doi: 10.1016/j.ejim.2023.11.013. Online ahead of print.

Authors

Tetiana Lapikova-Bryhinska¹, Stefano Ministrini¹, Yustina M Puspitasari¹, Simon Kraler², Shafeeq Ahmed Mohamed³, Sarah Costantino³, Francesco Paneni⁴, Michael Khetsuriani⁵, Susan Bengs¹, Luca Liberale⁶, Fabrizio Montecucco⁶, Wolfgang Krampla⁷, Peter Riederer⁸, Margareta Hinterberger⁹, Peter Fischer⁹, Thomas F Lüscher¹⁰, Edna Grünblatt¹¹, Alexander Akhmedov¹, Giovanni G Camici¹²

Affiliations

¹ Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland.
² Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Internal Medicine, Kantonspital Baden, Baden, Switzerland.
³ Center for Translational and Experimental Cardiology, University Hospital of Zurich, Zurich, Switzerland.
⁴ Center for Translational and Experimental Cardiology, University Hospital of Zurich, Zurich, Switzerland; University Heart Center, Cardiology, University Hospital Zurich, Zurich, Switzerland; Department of Research and Education, University Hospital Zurich, Zurich, Switzerland.
⁵ Department of General and Molecular Pathophysiology, Bogomolets Institute of Physiology NAS of Ukraine, Kyiv, Ukraine.
⁶ First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa 16132, Italy; IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, Genoa 16132, Italy.
⁷ Landesklinikum Korneuburg-Stockerau, Korneuburg, Austria.
⁸ Center of Mental Health, Clinic and Policlinic of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany; Department of Psychiatry, University of Southern Denmark Odense, Odense, Denmark.
⁹ Department of Psychiatry, Medical Research Society Vienna D.C., Danube Hospital Vienna, Vienna, Austria.
¹⁰ Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Royal Brompton and Harefield Hospitals and Imperial College, London, UK.
¹¹ Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH, Zurich, Switzerland.
¹² Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Research and Education, University Hospital Zurich, Zurich, Switzerland. Electronic address: giovanni.camici@uzh.ch.

PMID: 37981527
DOI: 10.1016/j.ejim.2023.11.013

Abstract

Introduction: Differential expression of long non-coding RNAs (lncRNAs) is a hallmark of cardiovascular aging, cerebrovascular diseases, and neurodegenerative disorders. This research article investigates the association between a panel of lncRNAs and the risk of death and ischemic stroke in a cohort of non-institutionalized elderly subjects.

Method: A total of 361 healthy individuals aged 75 years old, prospectively recruited in the Vienna Transdanube Aging (VITA) cohort, were included. Expression of lncRNAs at baseline was assessed using quantitative polymerase chain reaction PCR with pre-amplification reaction, using 18S for normalization. The primary endpoint was all-cause mortality; the secondary endpoint was the incidence of new ischemic brain lesions. Death was assessed over a 14-year follow-up, and ischemic brain lesions were evaluated by magnetic resonance imaging (MRI) over a 90-month follow-up. Ischemic brain lesions were divided into large brain infarcts (Ø≥ 1.5 cm) or lacunes (Ø< 1.5 cm) RESULTS: The primary endpoint occurred in 53.5 % of the study population. The incidence of the secondary endpoint was 16 %, with a 3.3 % being large brain infarcts, and a 12.7 % lacunes. After adjustment for potential confounders, the lncRNA H19 predicted the incidence of the primary endpoint (HR 1.194, 95 % C.I. 1.012-1.409, p = 0.036), whereas the lncRNA NKILA was associated with lacunar stroke (HR 0.571, 95 % C.I. 0.375-0.868, p = 0.006).

Conclusion: In a prospective cohort of non-institutionalized elderly subjects, high levels of lncRNA H19 are associated with a higher risk of death, while low levels of lncRNA NKILA predict an increased risk of lacunar stroke.

Keywords: Aging; Inflammation; Long non-coding RNAs; Neuronal plasticity; Oxidative stress; Stroke; Vascular dysfunction.