TL2: Cardio-Metabolic Disorders

Vascular diseases are the major cause of death worldwide, accounting for a combined 15 million deaths in 2015 being the leading cause of death globally over the past 15 years. Diabetes killed 1.6 million people in 2015, up from less than 1 million in 2000. Additionally, musculoskeletal conditions have significant impact on health and quality of life with a major burden on individuals, health and social care systems, with indirect costs being predominant. A failure in preventing and resolving inflammation is a common issue to these three chronic conditions that very often co-exist in the same individuals.

TL2 aims at capturing and measuring patient's complexity in the context of these comorbidities and particularly fostering innovative translational approaches to deeply understand their molecular causative mechanisms and find new useful biomarkers to establish an early diagnosis and novel therapies. TL2 aggregates both fundamental and clinical research with technology development, integrating four clinically-oriented RGs (RG10: Cardio-vascular Diseases; RG11: Reno-vascular Diseases; RG12: Diobesity; and RG13: Musculoskeletal Immune-Regulation) and the five technology-driven RGs (RG1-RG5), with all researchers involved are in continuous interaction with clinicians guaranteeing a translational perspective. For the near future we anticipate extending the interaction to other RGs and TLs to explore common molecular mechanisms, diagnostics and therapeutic strategies.

The clinical services involved are the Cardiology departments of CHLO and CHLC, Nephrology of CHLC, CHLO and HFF, Internal Medicine of CHLC, HFF and Hospital da Luz, Rheumatology of CHLO, and the APDP-Diabetes Portugal.

Researchers will explore, implement or develop in vivo models for inflammatory comorbidities (hypertension, dyslipidemia and insulin resistance induced by chronic intermittent hypoxia; genetic manipulated mice with heart hyperplasia and nodal dysfunction, diet induced metabolic diseases; autonomic/carotid body manipulation), cell-based strategies (generation and differentiation of iPS cells, reprogramming inflammatory T cells), advanced analytical approaches (lipid-, prote-, transcript- and metabol- omics) and molecular biology methodologies applied not only to the experimental models but also to human samples.

Collaborations within iN4H already originated promising results, such as:

detection of a new family of oxidized lipids in the blood - cholesteryl hemiesters - particularly relevant in the context of acute myocardial infarction and angina pectoris;
implementation of protocols for generation, quality-control and use of iPS cell lines for human patients;
detection of a new biomarker of kidney tubular damage - uNAC;
a novel strategy for deep phenotyping of diabetic patients based on organ disease state and also on organ communication;
identification of a pathogenic T cell population in the blood of rheumatoid arthritis patients which is not subdued by current therapies.