Ageing and microvasculature

Abstract

A decline in the function of the microvasculature occurs with ageing. An impairment of endothelial properties represents a main aspect of age-related microvascular alterations. Endothelial dysfunction manifests itself through a reduced angiogenic capacity, an aberrant expression of adhesion molecules and an impaired vasodilatory function. Increased expression of adhesion molecules amplifies the interaction with circulating factors and inflammatory cells. The latter occurs in both conduit arteries and resistance arterioles. Age-related impaired function also associates with phenotypic alterations of microvascular cells, such as endothelial cells, smooth muscle cells and pericytes. Age-related morphological changes are in most of cases organ-specific and include microvascular wall thickening and collagen deposition that affect the basement membrane, with the consequent perivascular fibrosis. Data from experimental models indicate that decreased nitric oxide (NO) bioavailability, caused by impaired eNOS activity and NO inactivation, is one of the causes responsible for age-related microvascular endothelial dysfunction. Consequently, vasodilatory responses decline with age in coronary, skeletal, cerebral and vascular beds. Several therapeutic attempts have been suggested to improve microvascular function in age-related end-organ failure, and include the classic anti-atherosclerotic and anti-ischemic treatments, and also new innovative strategies. Change of life style, antioxidant regimens and anti-inflammatory treatments gave the most promising results. Research efforts should persist to fully elucidate the biomolecular basis of age-related microvascular dysfunction in order to better support new therapeutic strategies aimed to improve quality of life and to reduce morbidity and mortality among the elderly patients.

Keywords: Endothelial cells; Endothelial dysfunction; Nitric oxide; Organ-specific ageing; Smooth muscle cells; Vascular remodelling.

Figure 1

Schematic representation of microcirculation components. The microcirculation is a network of small blood vessels, including arterioles, venules and capillaries. Blood flows from the arteries into the arterioles and then pass into the venules across true capillaries or throughfare channels and metarterioles (arteriovenous bypass). The precapillary sphincter, made of smooth muscle cells, controls blood flow into the true capillaries. As blood travels through the capillaries, plasma proteins and fluid enter the interstitial space according to hydrostatic and osmotic pressure gradients. Most of the fluid is reabsorbed into the post-capillary venules, while a fraction enters to the lymphatic circulation for its return to the blood circulation.

Figure 2

Schematic representation of biomolecular changes in age-related microvascular dysfunction. Oxidative stress plays a pivotal role in endothelial and myocitic impaired function.

Figure 3

Age-related changes of brain microvasculature. Post-mortem (myocardial acute infarction) histology studies on paraffin-embedded sections (5 μm thick) of formalin-fixed cerebral tissue. PAS staining of human brain gray matter, showing normal capillaries and arterioles in a young (A,C) compared to concentrically thickened microvessels in an aged man (B,D) mostly due to hyalinization (pink staining). Masson's trichrome staining shows normal microvessel in a young (E) and perivascular deposition of collagen (blue staining) around capillaries in an aged man (F). Immunohistochimical analysis for α-SMA shows normal arteriole in a young (G) and concentrically thickened arteriole due to an altered proliferation of smooth muscle cells in an aged man (H). Magnification 40×.

Figure 4

Microscopic aspects of human liver pseudocapillarisation. Post-mortem (myocardial acute infarction) histology studies on paraffin-embedded sections (5 μm thick) of formalin-fixed liver tissue. Masson's trichrome staining shows the central vein and pericentral hepatocytes of young (A) and old liver (B) with perisinusoidal collagen deposition (blue staining). CD31 immunostaining of young (C) and old liver (D) with an increased sinusoidal protein expression. Magnification 20×.

Figure 5

Ultrastructural aspects of age-related changes in rat kidney microvessels. Glomerular basement membrane of kidney in young (A) and old rat (B), that shows the characteristic thickening of capillary wall. Magnification 5000×. Cationized ferritin distribution on glomerular basement membrane of young (C) and old rat kidney (D). Magnification 30000×.

Figure 6

Ageing in skin microcirculation. Histology studies on paraffin-embedded sections (5 μm thick) of formalin-fixed skin of healthy subjects. Masson's trichrome staining shows collagen distribution (blue staining), around microvessels, in young (A) and old dermal skin (B). PAS staining shows hyaline deposits (pink staining), around microvessels, in young (C) and old dermal skin (D). CD31 immunostaining of young (E) and old dermal skin (F) showing the descrease of capillaries associated with ageing process. α-SMA immunostaining of young (G) and old dermal skin (H) showing the proliferation of VSMCs around aged microvessels. Magnification 40×.