Cardiovascular Research

Our group studies the molecu­lar mechanisms of cardiac injury, repair, and regeneration in myocardial infarction and heart fail­ure. We are particularly interested in the role of noncoding RNAs in the development and progression of heart failure. Our aim is to find new approaches for the treatment of heart failure and novel biomarkers for more personalized diagnostics and outcome prediction.

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Heart failure is an endpoint of multiple cardiovascular diseases, and its prognosis remains poor despite established drug therapies. A better understanding of the underlying pathophysiology is essential for the development of novel treatments and diagnostic tools for heart failure.

During the last decade, noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have emerged as key regulators of cardiovascular pathophysiology. We are currently investigating the mechanisms by which miRNAs and lncRNAs regulate the development and progression of heart failure. Our goal is to identify and characterize novel therapeutic targets that enhance cardiac repair and regeneration after injury. New treatment options could eventually improve the prognosis of heart failure.

Our studies bridge clinical and basic cardiovascular research. We use multi-omics analyses of heart failure patient samples to identify therapeutic targets and experimental models ranging from cardiac cell cultures to zebrafish heart failure models to characterize the function and therapeutic potential of candidate molecules.Unlike humans, zebrafish are capable of fully regenerating their heart and restoring cardiac function following injury, making them an excellent model organism for investigating factors regulating the development and recovery of heart failure.

Group leader

Päivi Lakkisto, MD, DrMedSci, docent
paivi.lakkisto@helsinki.fi

Group members

Ilkka Tikkanen, MD, PhD, professor
Mika Laine, MD, PhD, Adjunct Professor
Chunguang Wang, MD, PhD, Adjunct Professor
Jere Paavola, MD, PhD
Hong Wang, MSc, PhD
Mikko Hänninen, MD
Karri Kalervo, MD
Tuomas Mäntylä, MD
Suneeta Narumanchi, MSc
Heli Segersvärd, MD
Ian Hägerström, medical student
Katariina Immonen, BSc, research assistant
Sanni Perttunen, BSc, research assistant

We also study new biomarkers of heart failure. Cardiogenic shock (CS) is the most severe form of acute heart failure. In-hospital mortality is close to 40% even with current treatment. New biomarkers are urgently needed to stratify CS patients ac­cording to their risk and to optimize treat­ment. We previously demonstrated that miR-21-5p, miR-320a-3p, and miR-423- 5p are independent predictors of mortality in CS, highlighting the potential of ncRNAs as diagnostic and prognostic biomarkers. We are continuing CS biomarker studies in ongoing projects.

Group leader

Päivi Lakkisto, MD, DrMedSci, docent
paivi.lakkisto@helsinki.fi

Group members

Ilkka Tikkanen, MD, PhD, professor
Mika Laine, MD, PhD, Adjunct Professor
Chunguang Wang, MD, PhD, Adjunct Professor
Jere Paavola, MD, PhD
Hong Wang, MSc, PhD
Mikko Hänninen, MD
Karri Kalervo, MD
Tuomas Mäntylä, MD
Suneeta Narumanchi, MSc
Heli Segersvärd, MD
Ian Hägerström, medical student
Katariina Immonen, BSc, research assistant
Sanni Perttunen, BSc, research assistant

Selected publications

Lakkisto P, Dalgaard LT, Belmonte T, Pinto-Sietsma SJ, Devaux Y, De Gonzalo-Calvo D. Development of circulating microRNA-based biomarkers for medical-decision making: a friendly reminder of what should NOT be done. Crit Rev Clin Lab Sci 2023, 60:141-152. doi: 10.1080/10408363.2022.2128030

Wang H, Segersvärd H, Siren J, Perttunen S, Immonen K, Kosonen R, Chen YC, Tolva J, Laivuori M, Mäyränpää MI, Kovanen PT, Sinisalo J, Laine M, Tikkanen I, Lakkisto P. Tankyrase Inhibition Attenuates Cardiac Dilatation and Dysfunction in Ischemic Heart Failure. Int J Mol Sci. 2022; 23:10059. doi: 10.3390/ijms231710059

Wang C, Taskinen J, Segersvärd H, Immonen K, Kosonen R, Tolva JM, Mäyränpää MI, Kovanen PT, Olkkonen VM, Sinisalo J, Laine M, Tikkanen I, Lakkisto P. Alterations of cardiac protein kinases in cyclic nucleotide-dependent signaling pathways in human ischemic heart failure. Front Cardiovasc Med 2022, 9:919355. doi: 10.3389/fcvm.2022.919355

Narumanchi S, Wang H, Perttunen S, Tikkanen I, Lakkisto P, Paavola J. Zebrafish heart failure models. Front Cell Dev Biol 2021; 9:662583. doi: 10.3389/fcell.2021.662583

Hänninen M, Jäntti T, Tolppanen H, Segersvärd H, Tarvasmäki T, Lassus J, Vausort M, Devaux Y, Sionis A, Tikkanen I, Harjola V-P, Lakkisto P. Association of miR-21-5p, miR-122-5p and miR-320a-3p with 90-day mortality in cardiogenic shock. Int J Mol Sci 2020; 21:E7925; doi:10.3390/ijms21217925

Paavola J, Alakoski T, Ulvila J, Kilpiö T, Siren J, Perttunen S, Narumanchi S, Wang H, Lin R, Porvari K, Junttila J, Huikuri H, Immonen K, Lakkisto P, Magga J, Tikkanen I, Kerkelä R. Vezf1 regulates cardiac structure and contractile function. EBioMedicine 2020; 51:102608. Doi: 10.1016/j.ebiom.2019.102608

Jäntti T, Segersvärd H, Tarvasmäki T, Lassus J, Devaux Y, Vausort M, Pulkki K, Sionis A, Bayes-Genis A, Tikkanen I, Lakkisto P, Harjola V-P. Circulating levels of microRNA 423-5p are associated with 90-day mortality in cardiogenic shock. ESC Heart failure, 2019; 6: 98-102 

Kaartokallio T, Utge S, Klemetti MM, Paananen J, Pulkki K, Romppanen J, Tikkanen I, Heinonen S, Kajantie E, Kere J, Kivinen K, Pouta A, Lakkisto P, Laivuori H. Fetal microsatellite in the heme oxygenase 1 promoter is associated with severe and early-onset preeclampsia. Hypertension 2018; 71: 95-102.

Segersvärd H, Lakkisto P, Hänninen M, Forsten H, Siren J, Immonen K, Kosonen R, Sarparanta M, Laine M, Tikkanen I. Carbon monoxide releasing molecule improves structural and functional cardiac recovery after myocardial injury. Eur J Pharmacol 2018; 818: 57-66.

Dash SN, Narumanchi S, Paavola J, Perttunen S, Wang H, Lakkisto P, Tikkanen I, Lehtonen S. Sept7b is required for the subcellular organization of cardiomyocytes and cardiac function in zebrafish. Am J Physiol Heart Circ Physiol 2017; 312: H1085-H1095.

External funding

Aarne Koskelo Foundation
Finnish Cultural Foundation
Finnish Foundation for Cardiovascular Research
Finnish Foundation for Laboratory Medicine
Finnish Society of Clinical Chemistry
Medical Society of Finland
Medicinska Understödsföreningen Liv och Hälsa r.f.
Päivikki and Sakari Sohlberg Foundation
Research Funding of the Helsinki-Uusimaa Hospital District (state funding for university-level health research)

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