assessment-vascular-tone-responsiveness-using-isolated-mesenteric

Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues

Altered vascular tone responsiveness to pathophysiological stimuli contributes to the development of a wide range of cardiovascular and metabolic ...

University of Hong Kong

Lipocalin-2 is a pro-inflammatory molecule characterized by a highly diversified pattern of expression and structure-functional relationships. In vivo, this molecule exists as multiple variants due to post-translational modifications and/or protein-protein interactions. Lipocalin-2 is modified by polyamination, which enhances the clearance of this protein from the circulation and prevents its excessive accumulation in tissues. On the other hand, animal studies suggest that non-polyaminated lipocalin-2 (npLcn2) plays a causal role in the pathogenesis of obesity-associated medical complications. The present study examined the presence of npLcn2 in samples from healthy volunteers or patients with cardiac abnormalities and evaluated npLcn2 as a biomarker for cardiometabolic risk assessment.

Measuring non-polyaminated lipocalin-2 for cardiometabolic risk assessment.

Aged arteries are characterized by attenuated vasodilator and enhanced vasoconstrictor responses, which contribute to the development of diseases such as arterial hypertension, atherosclerosis and heart failure. SIRT1 is a longevity regulator exerting protective functions against vascular ageing, although the underlying mechanisms remain largely unknown.

Endothelial SIRT1 prevents age-induced impairment of vasodilator responses by enhancing the expression and activity of soluble guanylyl cyclase in smooth muscle cells.

Lipocalin-2 is not only a sensitive biomarker, but it also contributes to the pathogenesis of renal injuries. The present study demonstrates that adipose tissue-derived lipocalin-2 plays a critical role in causing both chronic and acute renal injuries. Four-week treatment with aldosterone and high salt after uninephrectomy (ANS) significantly increased both circulating and urinary lipocalin-2, and it induced glomerular and tubular injuries in kidneys of WT mice. Despite increased renal expression of lcn2 and urinary excretion of lipocalin-2, mice with selective deletion of lcn2 alleles in adipose tissue (Adipo-LKO) are protected from ANS- or aldosterone-induced renal injuries. By contrast, selective deletion of lcn2 alleles in kidney did not prevent aldosterone- or ANS-induced renal injuries. Transplantation of fat pads from WT donors increased the sensitivity of mice with complete deletion of Lcn2 alleles (LKO) to aldosterone-induced renal injuries. Aldosterone promoted the urinary excretion of a human lipocalin-2 variant, R81E, in turn causing renal injuries in LKO mice. Chronic treatment with R81E triggered significant renal injuries in LKO, resembling those observed in WT mice following ANS challenge. Taken in conjunction, the present results demonstrate that lipocalin-2 derived from adipose tissue causes acute and chronic renal injuries, largely independent of local lcn2 expression in kidney.

Article	Year
Measuring non-polyaminated lipocalin-2 for cardiometabolic risk assessment. ESC heart failure\| PubMed ID: 29154418	2017
Endothelial SIRT1 prevents age-induced impairment of vasodilator responses by enhancing the expression and activity of soluble guanylyl cyclase in smooth muscle cells. Cardiovascular research\| PubMed ID: 30165439	2018
Lipocalin-2 derived from adipose tissue mediates aldosterone-induced renal injury. JCI insight\| PubMed ID: 30185654	2018

Cuiting Luo

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