Zhichao Zhou Group

Cardiovascular complications are a major cause of morbidity and mortality in cardiometabolic diseases, placing patients at high risk for life-threatening events such as myocardial infarction and stroke. Despite their prevalence, the underlying mechanisms remain poorly understood, and current therapies and biomarkers are insufficient for effective prevention and risk prediction. Our group is dedicated to uncovering novel molecular drivers of cardiovascular dysfunction, with the goal of identifying actionable therapeutic targets and reliable biomarkers to improve cardiovascular outcomes in cardiometabolic disease.

Cardiovascular complications are major clinical challenges in cardiometabolic diseases such as type 2 diabetes and obesity, contributing significantly to global morbidity and mortality. Despite their prevalence, the underlying mechanisms remain incompletely understood, and there is a critical need for targeted therapies and reliable biomarkers to improve cardiovascular risk prediction and treatment.

A central and early driver of these complications is endothelial dysfunction, characterized by increased oxidative stress and reduced nitric oxide bioavailability—both of which impair vascular homeostasis. Our group investigates the molecular mechanisms within endothelial cells that contribute to endothelial dysfunction and atherosclerotic vascular disease, focusing on key regulatory molecules such as proteins, enzymes and non-coding RNAs (ncRNAs) that shape cardiovascular responses in cardiometabolic disease.

In parallel, we explore the role of circulating cells, particularly red blood cells (RBCs), in modulating endothelial function. Traditionally viewed as passive oxygen carriers, RBCs are now recognized as active participants in cardiovascular regulation. Our recent work has revealed a paradigm-shifting role for RBCs in cardiometabolic disease, demonstrating their contribution to endothelial dysfunction and their potential as a source of novel biomarkers.

RBCs are rich in diverse ncRNAs. Through high-throughput profiling and functional validation in clinical cohorts and disease models—including genetically modified animals—we investigate the expression and function of RBC-derived ncRNAs, and how extracellular vesicles released from RBCs deliver these molecules to the vascular wall, contributing to cardiovascular pathology.

Additionally, we study the role of RBC-derived ATP, which is released under hypoxic conditions and acts via purinergic signaling to regulate vascular tone. This ATP release is impaired in disease states such as type 2 diabetes and pulmonary arterial hypertension. We focus on RBC–vascular wall interactions via purinergic signaling in cardiometabolic disease and how they respond to hypoxia.

Our overarching goal is to uncover key molecular drivers of endothelial dysfunction and atherosclerotic vascular disease, both within the vascular wall and through its interaction with circulating cells. By identifying novel biomarkers and therapeutic targets, we aim to advance precision medicine approaches for improving cardiovascular outcomes in cardiometabolic disease.

Zhichao Zhou, MD PhD, Docent and Principal Researcher at Cardiology unit, Department of Medicine Solna, Karolinska Institutet, zhichao.zhou@ki.se

I am an Associate Professor in the Division of Cardiology, Department of Medicine Solna, at Karolinska Institutet. I lead a research team focused on translational cardiovascular research, with a particular emphasis on cardiometabolic disease-associated cardiovascular complications. I graduated from a medical school in China (2007) and obtained my Ph.D. degree in Department of Cardiology from Erasmus University Medical Center, Rotterdam, in the Netherlands (2013). Following postdoctoral training at West Virginia University and Karolinska Institutet (2014–2018), my research has centered on elucidating novel mechanisms underlying cardiovascular complications, and on identifying effective therapeutic strategies and reliable biomarkers for their prevention and risk prediction.

Commissions of trust:

Editorial board: Front Cardiovasc Med; Front Pharmacol; Purinergic Signal; ATVB (early career editorial board)

Guest editor: Front Cardiovasc Med 2022; Int J Hypertens 2019

Grant evaluation task for: UK Medical Research Council (MRC); Polish National Science Center; Health Research Council of New Zealand; Invest in Future (IiF) Paracelsus Medical University Salzburg; Swedish Research Council; Karolinska Institutet KID block grant

Journal reviewer for: J Am Coll Cardiol; Eur Heart J; Circ Res; Cardiovasc Res; Hypertension; Atherosclerosis; Br J Pharmacol; J Appl Physiol; Am J Hypertens; JACC Asia; Mol Cell Life Sci; J Diabetes; J Diabetes Res; Front Cardiovasc Med; Front Pharmacol; Purinergic Signal etc.

Zhichao Zhou, MD PhD, Group Leader, zhichao.zhou@ki.se

Tong Jiao, MD PhD, Postdoc, tong.jiao@ki.se

Álvaro Santana-Garrido, PhD, Postdoc, alvaro.santana.garrido@ki.se

Eftychia Kontidou, Ms, doctoral student, eftychia.kontidou@ki.se

Rawan Humoud, MD, doctoral student, rawan.humoud@ki.se

Marita Wallin, Biomedical analyst, marita.wallin@ki.se

2024-present: Committee member of Circulation and Respiration Network KIRCNET (KI) Link to the web

2023-present: Member of Swedish Cardiometabolic Network (SCAMN) (Sweden)

2022-present: Member of EU-CardioRNA COST Action (Europe)

2022-present: Committee member of Cardiovascular Research Seminar Series (KI)

2022-present: Member of the Strategic Research Program (SRP) Diabetes PI Group (KI)

2021-2023: Committee member of Inflammation and Immunology Network (KiiM) (KI)

2020-2023: Coordinator of KIRCNET (KI)

EFSD/Novo Nordisk Foundation

Swedish Research Council

Swedish Heart and Lung Foundation

Karolinska Institutet

EFSD/Novo Nordisk Foundation Future Leaders Award

Swedish Heart and Lung Foundation 120-year Jubilee Award

Swedish Heart and Lung Foundation Research Position

zhichao.zhou@ki.se

Erythrocyte-derived extracellular vesicles induce endothelial dysfunction through arginase-1 and oxidative stress in type 2 diabetes. Collado A, Humoud R, Kontidou E, Eldh M, Swaich J, Zhao A, Yang J, Jiao T, Domingo E, Carlestål E, Mahdi A, Tengbom J, Végvári Á, Deng Q, Alvarsson M, Gabrielsson S, Eriksson P, Zhou Z (co-senior author), Pernow J. J Clin Invest. 2025 Mar 20;135(10):e180900. PMID: 40111409

miR-210 as a therapeutic target in diabetes-associated endothelial dysfunction. Collado A, Jiao T, Kontidou E, Carvalho L, Chernogubova E, Yang J, Zacagnini G, Zhao A, Tengbom J, Zheng X, Rethi B, Alvarsson M, Catrina SB, Mahdi A, Carlström M, Martelli F, Pernow J, Zhou Z (Corresponding and senior author). Br J Pharmacol. 2025 Jan;182(2):417-431. PMID: 39402703

Red blood cells as potential materials for microRNA biomarker study: overcoming heparin-related challenges. Kontidou E, Humoud R, Chernogubova E, Alvarsson M, Maegdefessel L, Collado A, Pernow J, Zhou Z (Corresponding and senior author). Am J Physiol Heart Circ Physiol. 2024 Nov 1;327(5):H1296-H1302. PMID: 39422364

The long noncoding RNA THBS1-AS1 promotes cardiac fibroblast activation in cardiac fibrosis by regulating TGFBR1. Zhou J, Tian G, Quan Y, Kong Q, Huang F, Li J, Wu W, Tang Y, Zhou Z (Co-corresponding and senior author), Liu X. JCI insight 2023 8;6. PMID: 36787190

Therapeutic potential of sunitinib in ameliorating endothelial dysfunction in type 2 diabetic rats. Mahdi A, Jiao T, Tratsiakovich Y, Wernly B, Yang J, Östenson CG, Danser AHJ, Pernow J, Zhou Z (Corresponding and senior author). Pharmacology 2022 107;3-4 160-166. PMID: 34929688

Downregulation of erythrocyte miR-210 induces endothelial dysfunction in type 2 diabetes. Zhou Z (Corresponding author), Collado A, Sun C, Tratsiakovich Y, Mahdi A, Winter H, Chernogubova E, Seime T, Narayanan S, Jiao T, Jin H, Alvarsson M, Zheng X, Yang J, Hedin U, Catrina SB, Maegdefessel L, Pernow J. Diabetes 2022 71;2 285-297. PMID: 34753800

Erythrocytes induce endothelial injury in type 2 diabetes through alteration of vascular purinergic signaling. Mahdi A, Tratsiakovich Y, Tengbom J, Jiao T, Garib L, Alvarsson M, Yang JN, Pernow J, Zhou Z (Corresponding and senior author). Front Pharmacol 2020 11; 603226. PMID: 33390992

Red blood cell peroxynitrite causes endothelial dysfunction in type 2 diabetes mellitus via arginase. Mahdi A, Tengbom J, Alvarsson M, Wernly B, Zhou Z (Co-corresponding and senior author), Pernow J. Cells 2020 9;7. PMID: 32708826

Activation of A2A but not A2B receptors are involved in uridine adenosine tetraphosphate-induced coronary smooth muscle relaxation. Sun C, Jiao T, Merkus D, Duncker DJ, Mustafa SJ, Zhou Z (Corresponding and senior author). J Pharmacol Sci, 2019 Sep; 141(1):64-69. PMID: 31640919

Altered purinergic receptor sensitivity in type 2 diabetes-associated endothelial dysfunction and Up₄A-mediated vascular contraction. Mahdi A, Jiao T, Tratsiakovich Y, Yang J, Östenson CG, Pernow J, Zhou Z (Corresponding and senior author). Int J Mol Sci. 2018 Dec 7;19(12):3942. PMID: 30544633

Erythrocytes from patients with type 2 diabetes induce endothelial dysfunction via arginase I. Zhou Z (Corresponding author), Mahdi A, Tratsiakovich Y, Zahorán S, Kövamees O, Nordin F, Uribe Gonzalez AE, Alvarsson M, Östenson CG, Andersson DC, Hedin U, Hermesz E, Lundberg JO, Yang J, Pernow J. J Am Coll Cardiol 2018 72;7 769-780. PMID: 30092954

Divergent coronary flow responses to uridine adenosine tetraphosphate in atherosclerotic ApoE knockout mice. Teng B, Labazi H, Sun C, Yang Y, Zeng X, Mustafa SJ, Zhou Z (Corresponding and senior author). Purinergic Signal. 2017 Dec 13(4):591-600. PMID: 28929376

Altered purinergic signaling in uridine adenosine tetraphosphate-induced coronary relaxation in swine with metabolic derangement. Zhou Z, Sorop O, de Beer VJ, Heinonen I, Cheng C, Jan Danser AH, Duncker DJ, Merkus D. Purinergic signal 2017 13;3 319-329. PMID: 28540569

Uridine adenosine tetraphosphate is a novel vasodilator in the coronary microcirculation which acts through purinergic P1 but not P2 receptors. Zhou Z, Merkus D, Cheng C, Duckers HJ, Jan Danser AH, Duncker DJ. Pharmacol Res 2013 67;1 10-7. PMID: 23063485