TransCardio Research Areas
Valvular and Vascular Biology
Atherosclerosis
Atherosclerosis is a chronic inflammatory process triggered by accumulation of cholesterol-containing low-density lipoproteins (LDL) particles in the arterial wall. Major etiological factors include hyperlipidemia, hypertension, diabetes, and cigarette smoking, all of which are thought to initiate and promote vascular inflammation.
We study several aspects of atherosclerosis to identify key pathways and targets with therapeutic potential. Our studies in this field range from experimental models to epidemiological and biomarker studies. One focus pathway for our studies is the lipid mediators of inflammation and its resolution.
References:
- Translational opportunities of single-cell biology in atherosclerosis.
- The resolvin D1 receptor GPR32 transduces inflammation resolution and atheroprotection.
- Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities.
Valvular Heart Disease
The heart valves, which maintain a unidirectional cardiac blood flow, are covered by endothelial cells, and structurally composed by valvular interstitial cells and extracellular matrix. Valvular heart disease can be either stenotic, causing obstruction of the valvular flow, or regurgitant referring to a back-flow through the valve. The pathophysiological changes in valvular heart disease include for example lipid and inflammatory cell infiltration, calcification, neoangiogenesis, and extracellular matrix remodelling.
Our research on valvular heart disease span from molecular and cellular studies of valves and valve-derived cells to echocardiography research, biomarkers, and epidemiology.
References:
- Artificial Intelligence Models Reveal Sex-Specific Gene Expression in Aortic Valve Calcification.
- The tyrosine kinase inhibitor nilotinib targets the discoidin domain receptor DDR2 in calcific aortic valve stenosis.
- Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease Through the Resolvin E1 and ChemR23 Axis.
Cardiovascular Calcification
Arterial and valvular calcifications become more predominant with aging and may be associated with atherosclerosis and prevalent cardiovascular risk factors. Calcium phosphate precipitations promote a phenotypic shift in vascular smooth muscle and valvular interstitial cells toward an expression pattern of osteoblastic genes, which promote the active phase of mineralization. A line of defense systems protects arterial and valvular calcification. Given the major roles of phosphate in soft tissue calcification, phosphate mimetics and/or prevention of phosphate dissipation represent novel potential therapeutic approaches for arterial and valvular calcification.
References:
- From organic and inorganic phosphates to valvular and vascular calcifications.
- Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease Through the Resolvin E1 and ChemR23 Axis.
- The G-protein coupled receptor ChemR23 determines smooth muscle cell phenotypic switching to enhance high phosphate-induced vascular calcification.
Gastro-cardiology
The cardiovascular risk factor chronic systemic inflammation may reflect gastroenterological inflammatory conditions, such as inflammatory bowel disease and gastrointestinal infections, in particular, chronic Helicobacter pylori infection. Diagnosing and treating Helicobacter pylori to reduce the risk of cardiovascular events and gastrointestinal bleeding are currently under investigation. We have in addition shown that virulence factors carried by Helicobacter pylori are associated with smooth muscle cell calcification.
References:
- Helicobacter Pylori Virulence Factor Cytotoxin-Associated Gene A (CagA) Induces Vascular Calcification in Coronary Artery Smooth Muscle Cells.
- Gastro-Cardiology: A Novel Perspective for the Gastrocardiac Syndrome.
- Helicobacter pylori screening in clinical routine during hospitalization for acute myocardial infarction.
Resolution of Cardiovascular Inflammation
An appropriate immune response is crucial for protecting us against harmful stimuli, whereas a maladaptive immune response ultimately causes harm. Dysregulated chronic inflammation with a failure in the resolution of inflammation lead to persistent recruitment and activation of leukocyte subtypes, which fail to skew the immune response to adequate healing of the inflammatory site and for re-establishment of cardiovascular homeostasis. This resolution of inflammation is an active process of limiting inflammatory cell infiltration and favouring phagocytosis and efferocytosis for the removal of debris and apoptotic cells from the site of inflammation.
Resolution of atherosclerosis inflammation
Lipid mediators of inflammation are part of the effectors in the atherosclerotic immune activation However, there are also lipid mediators with the opposite action of limiting and terminating the atherosclerotic inflammation. In particular, the lipid mediators lipoxins and resolvins act as inflammation stop signals by actively promoting the resolution of inflammation. Translational Cardiology is focusing on the GPR18, GPR32, ChemR23, and LXA receptors for these proresolving lipid mediators to decipher their pharmacology and signalling pathways, in particular in atherosclerosis.
References:
- The resolvin D2 - GPR18 axis is expressed in human coronary atherosclerosis and transduces atheroprotection in apolipoprotein E deficient mice.
- The resolvin D1 receptor GPR32 transduces inflammation resolution and atheroprotection.
- ERV1/ChemR23 Signaling Protects Against Atherosclerosis by Modifying Oxidized Low-Density Lipoprotein Uptake and Phagocytosis in Macrophages.
Systemic Inflammation
Our studies on inflammatory biomarkers and the effects of systemic inflammation in relation to cardiovascular disease measures provide important information on the mechanisms behind how chronic inflammation and its failure to resolve contribute to cardiovascular disease.
References:
- Omega-3 to omega-6 fatty acid oxidation ratio as a novel inflammation resolution marker for metabolic complications in obesity.
- Antiphospholipid antibodies in patients with calcific aortic valve stenosis.
- Cardiovascular Autonomic Function Changes and Predictors During a 2-Year Physical Activity Program in Rheumatoid Arthritis: A PARA 2010 Substudy.
Immunomodulation and Cardiovascular Consequences in COVID-19
Translational Cardiology has translated active resolution of inflammation without immunosuppression to application in COVID-19. In a randomized controlled clinical trial performed by Translational Cardiology, omega-3 treatment through intravenous fish oil administration activated metabolic pathways towards lipid proresolving mediators. We also address the vascular effects associated with COVID-19 infection and its chronic consequences.
References:
- Immunomodulation by intravenous omega-3 fatty acid treatment in older subjects hospitalized for COVID-19: A single-blind randomized controlled trial.
- Decreased oxidative stress and altered urinary oxylipidome by intravenous omega-3 fatty acid emulsion in a randomized controlled trial of older subjects hospitalized for COVID-19.
- Endothelial dysfunction in COVID-19: a position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science.
Cardiovascular Risk and Prevention
Arterial stiffness
References:
- Fatty acid desaturase genetic variations and dietary omega-3 fatty acid intake associate with arterial stiffness.
- Cardiovascular Risk Factors and Hemodynamic Measures as Determinants of Increased Arterial Stiffness Following Surgical Aortic Valve Replacement.
- Differential Associations for Salivary Sodium, Potassium, Calcium, and Phosphate Levels with Carotid Intima Media Thickness, Heart Rate, and Arterial Stiffness.
Omega-3 fatty acids
References:
- Dose-Dependent Risk Reduction for Myocardial Infarction with Eicosapentaenoic Acid: a Meta-analysis and Meta-regression Including the STRENGTH Trial.
- Omega-3 Polyunsaturated Fatty Acids and the Resolution of Inflammation: Novel Therapeutic Opportunities for Aortic Valve Stenosis?
- Omega-3 fatty acids, cardiovascular risk, and the resolution of inflammation.