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Scientific

USC CiMUS researchers identify key mechanism that could reduce vascular calcification in diabetic patients

  • The study, published in the journal Cardiovascular Diabetology, suggests that improving levels of pyrophosphate, a potent natural inhibitor of vascular calcification, could be an effective approach to preventing cardiovascular complications in diabetic patients.
  • The protective effect of pyrophosphate also opens the door to the prevention and treatment of other pathologies related to vascular calcification, such as chronic kidney disease and certain premature ageing syndromes (progeria).

 

A team of researchers from the Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) at the University of Santiago de Compostela has published a study in the journal Cardiovascular Diabetology that could change the approach to the treatment of cardiovascular complications in people with diabetes. The research, led by CiMUS principal investigator Dr Ricardo Villa-Bellosta, reveals that elevated glucose levels in diabetic patients negatively affect the metabolism of extracellular pyrophosphate, a potent natural inhibitor of vascular calcification. This finding suggests a potential avenue for preventing calcification in arteries and other blood vessels in people with diabetes, a breakthrough with significant implications for cardiovascular health.

 

Vascular calcification

Vascular calcification is a condition in which calcium deposits build up on the walls of blood vessels, impeding blood flow and increasing the risk of serious cardiovascular disease. This complication is especially prevalent in people with diabetes and is associated with a higher mortality rate from events such as heart attacks and strokes. ‘Our research has shown that hyperglycaemia in diabetes can reduce levels of extracellular pyrophosphate, a natural inhibitor of vascular calcification, creating an environment prone to calcium accumulation in the arteries,’ explains Dr Villa-Bellosta.

The CiMUS team studied these effects in both cell and animal models, finding that extracellular pyrophosphate metabolism is severely impaired under conditions of high glucose. In the study models, high glucose levels led to a decrease in pyrophosphate production, while favouring an increase in phosphate, a factor that promotes calcification. This imbalance affects the body's natural mechanisms to prevent calcification and is exacerbated in patients with diabetes. ‘We identified that key enzymes in pyrophosphate metabolism are altered under conditions of hyperglycaemia, which significantly affects the body's ability to protect against vascular calcification,’ adds Villa-Bellosta.

 

Pyrophosphate, an important therapeutic target

The study also highlights the potential of pyrophosphate as a therapeutic target. According to the authors, intervening to restore or improve pyrophosphate levels could represent a novel and effective approach in the prevention of cardiovascular complications in diabetic patients. ‘Our findings open up a promising avenue to explore treatments aimed at restoring the pyrophosphate balance in the vascular system of diabetic patients,’ adds the researcher. ‘Administration of pyrophosphate or the use of inhibitors of its hydrolysis could effectively reduce the risk of calcification in these patients.’

 

Clinical implications and future research

The publication in Cardiovascular Diabetology reinforces the clinical importance of this work and its impact on the scientific community, as it points to an innovative therapeutic pathway that could benefit millions of people affected by diabetes-related cardiovascular complications. By restoring pyrophosphate levels, the propensity for vascular calcification could be reduced, potentially improving quality of life and reducing mortality in this population. The team suggests that the next step is to develop clinical trials to assess whether treatments that modulate pyrophosphate metabolism may be feasible and safe in people with diabetes.

In addition to diabetes, pyrophosphate has also shown protective effects in other pathologies related to vascular calcification, such as chronic kidney disease and certain premature ageing syndromes (progeria). These findings reinforce the importance of this natural inhibitor in vascular health and its potential as a target for preventive treatments. ‘Our study represents a milestone in the understanding of how alterations in pyrophosphate metabolism affect vascular health, and we hope it will drive new lines of research and development of innovative therapies for cardiovascular diseases related to diabetes and other pathologies,’ says Villa-Bellosta.

 

Funding and collaboration

This groundbreaking study has been made possible thanks to funding provided by the Spanish Ministry of Education and Science, the Xunta de Galicia, and the Spanish Society of Nephrology, as well as support from the Ramón y Cajal programme for senior research. ‘We are deeply grateful for the support of the institutions and research programmes that have made this project possible,’ says Dr. Villa-Bellosta. ‘We are proud to contribute from CiMUS and the University of Santiago de Compostela to the advancement of science in such a crucial field of research as cardiovascular health and diabetes.’

 

World Diabetes Day round table debate 

This advance was one of those addressed at the round table discussion organised by CiMUS today to coincide with the commemoration of World Diabetes Day. Specialists from the Singular Centre and IDIS took part in the debate to share the main challenges and advances in the management of this disease. The researchers Carlos Diéguez, Iria Gómez-Touriño, Miguel Ángel Martínez-Olmos, Ricardo Villa Bellosta and Rubén Nogueiras were in charge of addressing the close relationship between diabetes and obesity, cardiovascular diseases, immunology, endocrinology and nutrition.

The opening of the conference was attended by the Deputy Director General of University Scientific and Technological Promotion, Irene Bonome; the Director of the USC Department of Biochemistry, Jaime Gómez; the Director of the USC Department of Physiology, Juan Zalvide, and the Deputy Director of CiMUS, José Luis Labandeira.