| Serné EH, de Jongh RT, Eringa EC, et al. Microvascular dysfunction: a potential pathophysiological role in the metabolic syndrome. Hypertension 2007;50:204-211.
The microcirculation may be a target for prevention and treatment of the metabolic syndrome.
Microvascular dysfunction influences pressure and flow patterns and thereby affects not only peripheral vascular resistance, but also insulin-mediated changes in muscle perfusion and glucose metabolism. This article examines data concerning microvascular dysfunction as a potential explanation for the clustering of several metabolic syndrome components.
Metabolic syndrome risk factors confer an increased risk for type 2 diabetes and cardiovascular disease. Better understanding of the pathophysiology underlying this clustering of risk factors may open the way to novel therapeutic approaches specifically targeting its underlying causes. In this article, Serné et al consider recent data clarifying the part played by microvascular dysfunction in the association between obesity, hypertension, and impaired insulin-mediated glucose disposal.
The microcirculation
The microcirculation is often taken to refer to vessels <150 µm in diameter, but has also been defined as including all arterial vessels that respond to increasing pressure by a reduction in lumen diameter, i.e. the smallest arteries and arterioles, along with capillaries and venules. Such definitional elusiveness does not apply to the microcirculation’s functions, which are to optimize nutrient and oxygen supply within tissue, to avoid large fluctuations in hydrostatic pressure in the capillaries (which would disturb capillary exchanges), and to regulate peripheral vascular resistance.
Microvascular dysfunction in hypertension and obesity
Hypertension and obesity are marked by similar defects in the microcirculation. These include abnormal mechanisms regulating vasomotor tone, anatomic alterations in precapillary resistance vessels (e.g. increased wall-to-lumen ratio), and reduction in the number of arterioles or capillaries within the vascular beds of various tissues, such as skin and skeletal muscle.
Microvascular dysfunction as a cause of hypertension
Capillary density in various tissues correlates inversely with blood pressure in both hypertensive and normotensive subjects. Vessel rarefaction may play a part in the aetiology of high blood pressure. There is a body of evidence to suggest that microvascular abnormalities both result from and contribute to hypertension, and the microcirculation may maintain or even amplify an initial increase in blood pressure in a kind of “vicious circle”. Microvascular dysfunction may contribute to various kinds of end-organ damage, such as retinopathy, lacunar infarcts, microalbuminuria, and affect muscle perfusion and metabolism.
Microvascular dysfunction as a cause of insulin resistance
The haemodynamic action of insulin is dependent on a balance between its vasoconstrictor and vasodilator effects. Insulin’s ability to dilate skeletal muscle vasculature is impaired in various insulin-resistant states, such as hypertension, obesity, and type 2 diabetes. It has been suggested that distribution of blood flow in nutritive and nonnutritive vessels may affect insulin-mediated glucose uptake. Insulin mediates changes in muscle microvascular perfusion consistent with capillary recruitment, which is itself associated with changes in skeletal muscle glucose uptake. The effect of insulin on capillary recruitment may be attributable to insulin-mediated effects on precapillary arteriolar tone or arteriolar vasomotion (rhythmic fluctuations of microvascular blood flow) or both. The microcirculation plays an important role in regulating nutrient and hormone access to muscle, and it may be that an impairment in capillary recruitment hampers glucose uptake by muscle.
Insulin resistance, arterial stiffness, and microvascular function
Classic cardiovascular risk factors (age, hypertension, diabetes, smoking, elevated LDL-cholesterol) are determinants of arterial stiffness, which is itself an important cardiovascular risk factor. Fasting insulin concentration is positively correlated with several indexes of arterial stiffness, and epidemiological data suggest that insulin resistance and arterial stiffness are related. In addition, insulin exerts numerous effects on the vascular production and release of key regulators of vascular tone. The metabolic syndrome is known to be associated with increased age-related progression of aortic stiffness, which is accompanied by structural or functional remodeling of the microcirculation. Microvascular damage may result from increased aortic stiffness, or microcirculatory abnormalities may increase aortic stiffness. Conclusion
For Serné et al, microvascular function appears to explain the clustering of several components of the metabolic syndrome, such as insulin resistance, obesity, and hypertension (Figure 1). Also, defects in the microvasculature are involved in the end-organ damage associated with the metabolic syndrome. The microcirculation may, therefore, be a target for the prevention and treatment of the metabolic syndrome. The pathways of intracellular insulin signaling and obesity-related endocrine signaling should be explored further to develop targeted interventions for microvascular dysfunction.
Figure 1. Microvascular dysfunction may play a causative role in the association between the metabolic syndrome, hypertension, and insulin resistance.
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