Vascular inflammation in hypertension and diabetes: molecular mechanisms and therapeutic interventions

Abstract

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.

Plasma Vasoprotective Eicosanoid Concentrations in Healthy Greyhounds and Non‐Greyhound Dogs

“…Both hypertension and albuminuria are considered indicators of generalized vascular dysfunction and risk markers for development of renal and cardiovascular disease 6, 7. Similar to previous reports, the Greyhounds in this study had higher SP and urinary albumin concentrations compared to the non‐Greyhound dogs 5, 18.…”

“…Vascular dysfunction is characterized by impaired vasomotor response, increased vascular permeability, endothelial cell proliferation, inflammation, and platelet adhesion and aggregation 6. Hypertension and loss of glomerular permselectivity are recognized manifestations of generalized endothelial dysfunction in people and are predictors of increased risk for cardiovascular dysfunction, progressive renal disease, ischemic heart disease, stroke, and thrombotic microangiopathy 7, 8, 9, 10.…”

Biomarkers of inflammation and endothelial dysfunction as predictors of pulse pressure and incident hypertension in type 1 diabetes: a 20 year life-course study in an inception cohort

“…Epidemiological evidence to support the concept of arterial stiffness/widened pulse pressure and hypertension as a consequence of vascular/systemic inflammation has been controversial [11,[26][27][28][29]. Our findings are in agreement with previous studies showing that higher levels of CRP are related to hypertension and pulse pressure [26,[30][31][32][33][34][35].…”

Angiotensin Receptor Blockers: Pharmacology, Efficacy, and Safety

“…66 Circulating Biochemical Markers of Vascular Inflammation Angiotensin II has been identified in studies of tissues and experimental animals as a proinflammatory molecule that stimulates the formation of reactive oxygen species, resulting in the upregulation of inflammatory mediators such as the transcription factor NF-jB and increased formation of chemokines, C-reactive protein (CRP), and adhesion molecules and activation of T lymphocytes that contribute to both BP elevation and atherosclerosis. 2,3,67 An increase in circulating markers of inflammation have been documented in patients with hypertension, obesity, and diabetes, and one of these agents, CRP, has been reported to independently predict CV risk. 68 In this context, ARBs along with other RAS blockers should be ideal drugs to block these proinflammatory actions of angiotensin II with a consequent reduction in the levels of circulating markers of inflammation.…”

“…In certain humans, however, inappropriate or exaggerated activity of the RAAS contributes to the development of hypertension and the initiation of a molecular cascade in tissues with consequent injury to critical organs such as the brain, kidneys, heart, and blood vessels. [1][2][3] As understanding of the pathologic role of the RAAS in hypertensive vascular disease has unfolded during the past century, so has the interest in developing drugs that could interdict specific components of the RAAS. The first of the RAAS-blocking drugs to become commercially available were the aldosterone antagonists in the 1970s, followed by the angiotensin-converting enzyme (ACE) inhibitors in the 1980s and the angiotensin II receptor blockers (ARBs) in the 1990s.…”