Dataset Information

Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins.

ABSTRACT:

Introduction

Shrunken pore syndrome (SPS), originally defined by cystatin C-based estimated glomerular filtration rate (eGFR_{cystatin C}) being less than 60% of creatinine-based estimated glomerular filtration rate (eGFR_creatinine) in the absence of extrarenal influences on the plasma levels of cystatin C or creatinine, is associated with a high increase in mortality, even in the absence of reduced glomerular filtration rate (GFR). The objective of the present study was to determine whether the proteome of patients with SPS shows differences from that of patients with normal or reduced measured GFR (mGFR) without SPS.

Methods

Four patient cohorts were included: 1 cohort with normal mGFR without SPS, 1 with normal mGFR with SPS, 1 with reduced mGFR without SPS, and 1 with reduced mGFR with SPS. The plasma levels of 177 selected proteins were analyzed.

Results

Differences in the levels of 30 proteins were specific for SPS; 31 differences were specific for patients with both SPS and reduced mGFR; and 27 were specific for reduced mGFR. Eighteen of the differences specific for SPS concerned proteins described as promoting, or being associated with, atherosclerosis. Twelve of the differences specific for patients with both SPS and reduced mGFR and 10 of the differences specific for reduced mGFR also concerned proteins described as promoting, or being associated with, atherosclerosis. Almost all (82 of 88) of the concentration differences represented increased levels. For SPS, but not for reduced mGFR, a correlation between protein size and increase in level was observed, with smaller proteins being associated with higher levels.

Conclusion

The high mortality in shrunken pore syndrome might be caused by the accumulation of atherosclerosis-promoting proteins in this condition.

SUBMITTER: Almen MS

PROVIDER: S-EPMC6308389 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins.

Almén Markus Sällman MS Björk Jonas J Nyman Ulf U Lindström Veronica V Jonsson Magnus M Abrahamson Magnus M Vestergren AnnaLotta Schiller AS Lindhe Örjan Ö Franklin Gary G Christensson Anders A Grubb Anders A

Kidney international reports 20180913 1

<h4>Introduction</h4>Shrunken pore syndrome (SPS), originally defined by cystatin C-based estimated glomerular filtration rate (eGFR<sub>cystatin C</sub>) being less than 60% of creatinine-based estimated glomerular filtration rate (eGFR<sub>creatinine</sub>) in the absence of extrarenal influences on the plasma levels of cystatin C or creatinine, is associated with a high increase in mortality, even in the absence of reduced glomerular filtration rate (GFR). The objective of the present study w ...[more]

PMID: 30596170

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Project description:BackgroundEndothelial lipase (EL), a new member of the lipase family, has been shown to modulate high-density lipoprotein (HDL-C) metabolism and atherosclerosis in mouse models. We hypothesized that EL concentrations would be associated with decreased HDL-C and increased atherosclerosis in humans.Methods and findingsHealthy individuals with a family history of premature coronary heart disease (n = 858) were recruited as part of the Study of the Inherited Risk of Atherosclerosis. Blood was drawn in the fasting state before and, in a subgroup (n = 510), after administration of a single dose of intravenous heparin. Plasma lipids were measured enzymatically, lipoprotein subclasses were assessed by nuclear magnetic resonance, and coronary artery calcification (CAC) was quantified by electron beam computed tomography. Plasma EL mass was measured using a newly developed enzyme-linked immunosorbent assay. Median EL mass in pre-heparin plasma was 442 (interquartile range = 324-617) ng/ml. Median post-heparin mass was approximately 3-fold higher, 1,313 (888-1,927) ng/ml. The correlation between pre-heparin EL mass and post-heparin EL mass was 0.46 (p < 0.001). EL mass concentrations in both pre- and post-heparin plasma significantly correlated with all NCEP ATPIII-defined metabolic syndrome factors: waist circumference (r = 0.28 and 0.22, respectively, p < 0.001 for each), blood pressure (r = 0.18 and 0.24, p < 0.001 for each), triglycerides (r = 0.22, p < 0.001; and 0.13, p = 0.004), HDL cholesterol (r = -0.11, p = 0.002; and -0.18, p < 0.001), and fasting glucose (r = 0.11 and 0.16, p = 0.001 for both). EL mass in both routine (odds ratio [OR] = 1.67, p = 0.01) and post-heparin (OR = 2.42, p = 0.003) plasma was associated with CAC as determined by ordinal regression after adjustment for age, gender, waist circumference, vasoactive medications, hormone replacement therapy (women), and established cardiovascular risk factors.ConclusionsWe report, to our knowledge for the first time, that human plasma EL concentrations, in both post-heparin and routine pre-heparin plasma, are significantly associated with metabolic syndrome features and with subclinical atherosclerosis. EL may be a pro-atherogenic factor in humans, especially in overweight individuals and those with metabolic syndrome.

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Dataset Information

Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins.

Introduction

Methods

Results

Conclusion

Publications

Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins.

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