Prof Göran Hansson, Head of the Cardiovascular Research Laboratory at the Centre for Molecular Medicine Karolinska University Hospital, Sweden, speaks with Cardio Debate & Radcliffe Cardiology about Inflammation in Atherogenesis and Plaque Disruption during the “Advances in the Pathogenesis and Management of Cardiovascular Disease” 2015 meeting, organised by the Cardiovascular Sciences Research Centre of St George’s University and held at the Royal College of Surgeons of England in London, UK.
What makes inflammation such an appealing hypothesis in atherogenesis?
Inflammation is present in the atherosclerotic lesion, together with cholesterol derived from lipoproteins and components from the vessel wall itself.
Cholesterol is a great risk factor, very important as is high blood pressure. But they cannot, alone, explain the disease process that we see. The disease is not only an accumulation of cholesterol, but a response of the tissue that includes inflammatory cells, immune cells. And therefore inflammation is a crucial component of this disease.
But we don’t understand enough about how it operates, but it’s there. It’s a fact.
What is the role of macrophages in plaque distribution?
Macrophages, activated macrophages, are found at sites of plaque disruption, and they make molecules – enzymes – that can chop up components of the fibrous plaque. So therefore the macrophage is unlikely to illicit plaque disruption by weakening the plaque by chopping up the collagen components so that the plaque is fragile and vulnerable and therefore cracks when it is hit by the force of the blood pressure.
What roles do lymphocytes play in this context?
The T-lymphocytes, which are the main type of lymphocytes present at these sites in the plaque – they are really the conductors of the orchestra of inflammation.
The T-cell can tell the monocyte or macrophage to become activated. Other types of T-cells can inhibit macrophage activation. So the T-cell can really control the whole process. And we do find activated T-cells as well as activated macrophages, at the site of plaque rupture.
Furthermore, the T-cell makes cytokines that inhibit collagen formation and smooth muscle accumulation and therefore they reduce cap formations. They both act on the vascular components – the cap and the macrophage, and they really control the disease process in that way.