Five major issues and goals for research within the field of circulation and metabolism have been defined, please see Figure. The goals represent areas where CircM scientists are expected to exhibit high levels of creativity during the five-year period. The goals overlap with one another and an overall aim is “goal synergy” referring to positive interactions or convergence among the five goals.
Aim: To explore vulnerability and its impact on cardiovascular disease
Vulnerability is a major determinant of risk and can be described as the weakness or gap in our protection efforts. Vulnerability gives rise to risk. Examples of research questions that cover objectives to reach the goal are:
- Individuals with genetic predisposition, e.g. ion channel mutation
• Who will develop lethal arrhythmia?
- Individuals with asymptomatic atherosclerosis
• Who will develop symptomatic disease?
- Patients with acute coronary syndrome
• Who will suffer from new events? Who is not responding to therapy, and why not?
- Patients on anticoagulant/antiplatelet therapy
• Who will suffer a major bleed?
- Population-based cohorts – vulnerability to develop cardiovascular disease
• What is the combined influence of psychology and biology in vulnerable individuals?
• Who is susceptible to environmental exposures?
• Impact of covid-19 pandemia on vulnerable individuals?
Aim: To characterize inflammatory metabolic conditions and explain cardiometabolic risk
Type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), obesity/overweight and atherosclerosis can be collectively termed as “inflammatory metabolic conditions”. They constitute a rapidly growing threat to global human health. Examples of research questions that cover objectives to reach the goal are:
- What is the impact of ectopic fat depots on metabolic dysfunction and cardiovascular disease (e.g. atrial fibrillation and myocardial fibrosis)?
• epicardial and periarterial fat
• subcutaneous vs visceral fat
• hepatic fat
- What is the influence of diet?
• immunometabolic regulation
• nutritional quality vs nutrition information
- Comprehensive diabetes studies
• from mathematical models to prospective databases
III. Vascular integrity
Aim: To understand why and when impaired vascular integrity leads to clinical manifestations
Loss of vascular integrity, defined as breakdowns in the vasculature's functions and regenerative abilities, can lead to serious consequences. Still, to measure vascular alteration and understand its association with cardiovascular complications remains a challenge. Examples of research questions that cover objectives to reach the goal are:
- How can we improve the quantification and characterization of atherosclerotic plaques?
- Can we identify potential determinants of plaque vulnerability?
- What is the role of dysfunctional microcirculation in subclinical and manifest disease?
• skin microcirculatory function
• retinal angiogenesis
- Investigation of other vascular abnormalities (that remain little studied)
• spontaneous coronary artery dissection
• dilation of aorta
- Novel insights into blood pressure regulation in health, disease and exercise
IV. Cardiac functionality
Aim: To explore pathways enabling maintenance and restorance of cardiac function
Cardiac dysfunction can develop silently as a consequence of metabolic dysfunction or be the result of acute myocardial ischemia and mechanical stress. It also plays a major role in multi-organ failure. Examples of research questions that cover objectives to reach the goal are:
- What is the relation between structural and functional characteristics of myocardial tissue?
- Is cardiac dysfunction associated with subclinical and manifest cardiometabolic disease?
• cardiac remodeling
• myocardial fibrosis
- How is cardiac function affected by surgery and inflammatory assaults?
• heart valve surgery
• non-cardiac surgery
Aim: To develop new methodologies and thereby create unique possibilities to answer the research questions raised in goals I – IV
One of CircM´s major strengths is the high potential to establish translational activities that connect the medical field with latest technology. Examples of methodological research projects that cover objectives to reach the goal are:
- Integration of existing biobanks
- Creation of new biobanks
• integration with ”Hälsosamtalet”, quality registries, etc
- Frontline diagnostic imaging
• photon counting computed tomography
• tailor-made nanoprobes
• magnetic resonance imaging
• biomedical optics
- Modeling, simulation and artificial intelligence
• development and clinical evaluation of digital twins
• integration of metabolic, functional and anatomic data for personalized care and prevention
• experimental models of thrombosis
• health economic modeling