Arterial Stiffness, Endothelial Function and Novel Pharmacological Approaches

Abstract

1. Despite over half a century of intensive research, cardiovascular disease remains the leading cause of death world wide. Nevertheless, a number of risk factors for cardiovascular disease have been identified, such as hypertension and serum cholesterol, and therapies targeting such factors are effective in reducing cardiovascular and total mortality. Arterial stiffness is an additional independent risk factor for cardiovascular disease and strategies aimed at lowering arterial stiffness may be effective in reducing cardiovascular risk. However, in order to exploit fully the therapeutic potential of this approach, it is necessary first to understand the physiological and pathophysiological factors regulating the stiffness of the large arteries. 2. Until recently, stiffness was thought to depend largely upon structural components within the arterial wall, such as elastin and collagen and the distending pressure. However, we now recognize that arterial smooth muscle also regulates vessel stiffness and that a number of locally derived and circulating factors, including nitric oxide (NO), endothelin-1 and the natriuretic peptides, contribute to the short-term or functional regulation of large artery stiffness. Changes in the balance between these factors and, in particular, a reduction in NO production may well explain why conditions such as hypercholesterolaemia and diabetes are themselves associated with arterial stiffening before the development of manifest atherosclerosis. 3. The importance of smooth muscle in regulating arterial stiffness suggests that direct pharmacological manipulation of stiffness may be possible, thus providing novel therapeutic strategies to reduce cardiovascular risk. Furthermore, differences in the effect of existing drugs on larger artery stiffness may explain, in part, why some drugs produce better clinical outcomes than others.

Pulsatile Arterial Pressure (Pap) and Vascular Remodelling Indices: Search of Early Symptoms of Cardiovascular Pathology in Children

“…Так, с увеличением общего периферического сосудистого сопротивления наблюдается рост уровня ДАД, а с увеличе-нием жесткости артерий -его снижение. В этих условиях уровень ПАД, представляющий собой разницу САД и ДАД, увеличивается [20][21][22]. В настоящем исследовании наряду с положительной связью значений ПАД и САД была обнару-жена значимая отрицательная связь значений ПАД и ДАД, причем в группе детей с повышенным ИМТ.…”

“…У взрослых увеличение ПАД ассоциировано с суще-ственным ростом ССЗ и смертности [11,13,23], что в значительной мере обусловлено увеличением жесткости артериальной стенки [21,24,25]. Мы не зафиксировали корреляции значений индикатора жесткости сосудистой стенки (СРПВ с ПАД) в группе детей с повышенным ИМТ.…”

Circulating Chemerin Level is Independently Correlated with Arterial Stiffness

“…Arterial stiffness is recognized as a result of structural and functional changes of the vascular tree 22) . Vascular endothelium plays an important role in the functional regulation of arterial stiffness by secreting nitric oxide, endothelin-1, and natriuretic peptides 23) . Endothelial dysfunction is an early and potentially reversible event in atherogenesis 24) .…”

The influence of obesity on arterial compliance in adult men and women

“…6,12 This supports the idea that obesity may be influential in the pathology of declining arterial compliance, thereby increasing the risk for atherosclerotic plaque formation. 24 This study also suggests that obesity may alter large and small arterial compliance even after adjusting for the presence of hypertension and hyperlipidemia. Other studies have shown similar associations between obesity and arterial compliance in younger populations, providing evidence that vascular deterioration begins to occur at a young age.…”

“…A reduction in arterial compliance has been attributed to structural changes, such as elastin fragmentation and degeneration, increases in collagen, and thickening of the vessel wall, 25 as well as endothelial dysfunction. 24 One potential mechanism is that excess adipose tissue increases circulating levels of interleukin-6, C-reactive protein, and tumor necrosis factor-␣, 7 leading to endothelial dysfunction and development of athero-or arteriosclerosis. 26 A second proposed mechanism is obesity-induced insulin resistance.…”