Endothelial and microvascular function in liver cirrhosis: an old concept that needs re-evaluation?

Abstract

Liver cirrhosis is characterized by significant circulatory dysregulation, related to an imbalance among several vasodilating agents, mainly nitric oxide. In contrast to portal vein and macrovascular hemodynamic alterations, which have been rather well described, the peripheral microcirculatory and endothelial structure and function in this population are less well studied. Endothelial dysfunction is characterized by an imbalance between endothelium-derived relaxing and contracting factors. A number of methods have been used to assess endothelial and microvascular function in human studies. Venous occlusion plethysmography was used for many years as the gold standard for evaluating endothelial function, but flow-mediated dilatation (FMD) of the forearm is currently the most frequently used method. In patients with cirrhosis, the few existing studies have mainly used FMD, but the relevant results are largely contradictory. In recent years, several noninvasive and easily applicable methods, such as near-infrared spectroscopy, laser speckle contrast imaging, peripheral arterial tonometry, optical coherence tomography and nailfold video-capillaroscopy, have been increasingly used to assess peripheral microvascular function and have demonstrated a number of advantages. In this review, we present functional methods to evaluate peripheral microvascular and endothelial function, and we discuss the existing evidence on circulatory dysfunction in patients with liver cirrhosis.

Oxidative Mechanisms and Cardiovascular Abnormalities of Cirrhosis and Portal Hypertension

“…The decrease in peripheral vascular resistance is thought to be due to an imbalance between vasoconstrictive and vasodilatory factors. The former is mainly driven by the sympathetic system [14], renin-angiotensin system (RAS) [15], endothelin-1 [16], and thromboxane [17]; the latter by glucagon [18], prostaglandins [19], bile acids, nitric oxide (NO) [20], carbon monoxide (CO) [21], and hydrogen sulfate (H 2 S) [22]. Although the vasoconstrictors such as the sympathetic system [23,24] and RAS [25,26] are increased in subjects with cirrhosis, the response of cirrhotic subjects to vasoconstrictors as a whole is impaired [27].…”

Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis

“…This process is called bacterial translocation [6,[11][12][13][14] and leads to the development of local (in the intestinal wall, liver, and blood vessels) and systemic inflammation. The inflammatory environment contributes to the dysfunction of the endothelium, which begins to secrete substances that cause vasodilation (nitric oxide) and vasoconstriction (endothelin-1), and inhibits the formation of vasodilating nitric oxide (asymmetric dimethylarginine [ADMA]) [15][16][17][18]. Dysregulated dilatation of intestinal blood vessels leads to increased splanchnic blood flow, which, together with an increase in ADMA in the portal system resulting in increased vascular resistance to portal blood flow, worsens portal hypertension [15][16][17][18].…”

“…The inflammatory environment contributes to the dysfunction of the endothelium, which begins to secrete substances that cause vasodilation (nitric oxide) and vasoconstriction (endothelin-1), and inhibits the formation of vasodilating nitric oxide (asymmetric dimethylarginine [ADMA]) [15][16][17][18]. Dysregulated dilatation of intestinal blood vessels leads to increased splanchnic blood flow, which, together with an increase in ADMA in the portal system resulting in increased vascular resistance to portal blood flow, worsens portal hypertension [15][16][17][18]. This dysregulated splanchnic vasodilation results in a compensatory increase in the work that the heart carries out (hyperdynamic circulation), which further exacerbates the above-mentioned disorders, forming a positive feedback loop [6].…”