Association Between Circulating Endostatin, Hypertension Duration, and Hypertensive Target-Organ Damage

Abstract

Abstract-Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive targetorgan damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with ≥5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001).In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage.

Endostatin, Cathepsin S, and Cathepsin L, and Their Association with Inflammatory Markers and Mortality in Patients Undergoing Hemodialysis

“…The endostatin levels were about five-fold higher in the present study as compared with elderly individuals in the general population [28], which may partly be explained by the fact that endostatin has been shown to be associated with many risk factors that are highly prevalent in HD patients: gluco-metabolic disturbance [31,32], elevated blood lipids [33], and long term hypertension [28]. The high levels may in HD patients may additionally be explained by the fact that urinary excretion is the major elimination route of endostatin [34].…”

“…Elevated endostatin levels have been suggested as a biomarker of a rapid turnover of the extracellular matrix in patients with malignant diseases, such as renal carcinoma [27], and in patients with hypertensive renal disease [28]. Yet, initiated extra cellular matrix remodeling has been shown to be present already in early CKD stages [10,27,29], and may thus progress further during HD.…”

“…Previous studies have shown that conventional hemodialysis with lowflux membranes effectively eliminates small molecules such as urea and creatinine but do not reduce the levels of proteins in the 20-30 kDa range. Post-dilution haemodiafiltration and predilution haemofiltration reduced cystatin C (13.3 kDa) and beta2-microglobulin (11.8 kDa) but was less efficient for removing beta-trace protein (23)(24)(25)(26)(27)(28)(29) [36]. Cathepsin S, cathepsin L and endostatin are in the same molecular range as beta-trace protein which means that these dialysis methods will not reduce the plasma levels.…”

Endostatin Level is Associated with Kidney Injury in the Elderly: Findings from Two Community-Based Cohorts

“…Yet to date, reports on the role of collagen XVIII and endostatin in the development of renal impairment from community-based surveys are limited. We recently reported that serum endostatin was associated with the urinary albumin/creatinine ratio in elderly individuals with hypertension, suggesting that endostatin may be a biomarker of, or causally involved, in the pathophysiology of hypertensive kidney damage [14]. …”

172: Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers

“…Especially, the elderly appeared to have high serum endostatin levels in the absence of CRC. The mechanism of such age-related increase in endostatin levels is unknown, but it might be associated with age-related increase in cardiovascular disease and the elevated endostatin levels in these patients (Mitsuma et al, 2007;Carlsson et al, 2013). Li et al, 2012 have reported that increased serum endostatin levels correlate with CRC progression.…”