Association of urinary peptides with hypertension

BACKGROUNDHypertension is a common condition worldwide, yet its underlying mechanisms remain largely unknown. This study aims at identifying urinary peptides associated with hypertension to further explore its molecular pathophysiology. METHODSPeptidome data from 2876 individuals without end-organ damage were retrieved from the Human Urinary Proteome Database general population (discovery) or type 2 diabetic (validation) cohorts. Participants were divided based on systolic and diastolic blood pressure (SBP and DBP) into hypertensive (SBP[&ge;]140mmHg and/or DBP[&ge;]90mmHg) and normotensive (SBP<120mmHg and DBP<80mmHg, without antihypertensive treatment) groups. Differences in peptide abundance between the two groups were confirmed using an external cohort (n=420) of participants without end-organ damage, matched for age, body-mass index, eGFR, sex and presence of diabetes. Further, associations of the peptides with BP as a continuous variable were investigated. Findings were compared with peptide biomarkers of chronic diseases and bioinformatics analyses were conducted to potentially highlight the underlying molecular mechanisms. RESULTSBetween hypertensive and normotensive individuals, ninety-six (mostly COL1A1 and COL3A1) peptides were found significantly different in the discovery (adjusted) as well as the validation (nominal significance) cohorts with consistent regulation. Of these peptides, 83 were also consistently regulated in the matched cohort. A weak, yet significant association between their abundance and standardized BP was also observed. CONCLUSIONSHypertension is associated with an altered urinary peptide profile, with evident collagen differential regulation. Peptides related to vascular calcification and sodium regulation are also affected. Whether these modifications reflect the pathophysiology of hypertension per se and/or early subclinical target organ damage warrants further investigation. Novelty and RelevanceO_ST_ABSWhat is New?C_ST_ABSThis is the first study demonstrating differential regulation of urinary peptides in hypertensive patients, independent from other co-factors like age, diabetes, or established kidney or cardiovascular disease. What is Relevant?The observed changes in urinary peptides indicate individual differences in molecular changes observed in hypertension, and may guide personalized treatment based on the observed molecular changes Clinical/Pathophysiological Implications?The results indicate that collagen homeostasis may be a key molecular feature in hypertension and may serve as an attractive mechanism for pharmacological intervention.