Collaborative European study finds immune cells which protect against heart disease

Atherosclerosis, an accumulation of fat and inflammation in arteries, causes myocardial infarction and stroke, two deadly complications. The risk factors for atherosclerosis are well known and include hypercholesterolemia, smoking, diabetes and high blood pressure. Protective factors may also be important in atherosclerosis but are poorly understood. A new study published in this month´s issue of Nature Medicine presents the discovery of such a protective mechanism, which could be of great importance for future therapy.

A collaborative effort organized within the European Vascular Genomics Network (EVGN) has identified a subpopulation of T lymphocytes (called natural T regulatory cells, or Treg), which inhibit the formation of atherosclerotic plaques. Drs. Alain Tedgui and Ziad Mallat of INSERM U689 in Paris and Dr. Goran Hansson of Karolinska Institute´s Center for Molecular Medicine in Stockholm led two of the research teams in the study.

The senior author of the study Dr. Ziad Mallat explains the theory behind the study: “We postulated that in atherosclerosis there is an imbalance between regulatory and pathogenic immunity, and that such a disequilibrium promotes both plaque development and plaque inflammation”.

“We tested our hypothesis in a mouse model of the human disease, explains Mallat. “If these Treg were absent, the animals developed bigger atherosclerotic lesions. But when we injected the Treg cells they could turn off the atherosclerotic process”.

Further support for a controlling role of Treg in atherosclerosis came when the scientists inactivated these cells by injecting antibodies that blocked their activity. “We observed – says Dr. Alain Tedgui, President of EVGN and head of the Paris group – that antibody-treated mice – where the Treg were sort of handcuffed and hence unable to do their job – developed bigger lesions than their control counterparts.”

The scientists went one step further and identified a key molecule which is made by Treg and inhibits atherosclerosis. “Gene technology made it possible for us to turn off a signalling molecule called TGF-beta”, says Dr Goran Hansson. “The Treg cells then lost their protective activity. This tells us that TGF-beta is an important tool by which Treg protect against atherosclerosis.”

Dr Alain Tedgui now sees interesting opportunities for cardiovascular medicine: “Early that it might be, it is reasonable to consider novel kinds of therapies based on regulatory immune cells”.

EVGN is a network of excellence funded through the European Union Research Programme.