Vascular inflammation in hypertension and diabetes: molecular mechanisms and therapeutic interventions.
More than 80% of patients with type 2 diabetes mellitus develop hypertension, and approx. 20% of patients with hypertension develop diabetes. This combination of cardiovascular risk factors will account for a large proportion of cardiovascular morbidity and mortality. Lowering elevated blood pressure in diabetic hypertensive individuals decreases cardiovascular events. In patients with hypertension and diabetes, the pathophysiology of cardiovascular disease is multifactorial, but recent evidence points toward the presence of an important component dependent on a low-grade inflammatory process. Angiotensin II may be to a large degree responsible for triggering vascular inflammation by inducing oxidative stress, resulting in up-regulation of pro-inflammatory transcription factors such as NF-kappaB (nuclear factor kappaB). These, in turn, regulate the generation of inflammatory mediators that lead to endothelial dysfunction and vascular injury. Inflammatory markers (e.g. C-reactive protein, chemokines and adhesion molecules) are increased in patients with hypertension and metabolic disorders, and predict the development of cardiovascular disease. Lifestyle modification and pharmacological approaches (such as drugs that target the renin-angiotensin system) may reduce blood pressure and inflammation in patients with hypertension and metabolic disorders, which will reduce cardiovascular risk, development of diabetes and cardiovascular morbidity and mortality.
Savoia
Carmine
C
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, QC, Canada.
Schiffrin
Ernesto L
EL
D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D048909:Diabetes Complications / Q000276:immunology / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D014657:Vasculitis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism
D015815:Cell Adhesion Molecules; D016207:Cytokines; D016328:NF-kappa B; D000804:Angiotensin II; D000450:Aldosterone