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A Multi-Omics Approach to Defining Target Organ Injury in Youth with Primary Hypertension
Kalyani Ananthamohan1, Tammy M Brady2, Mohammed Arif1
1Department of Internal Medicine, Division of Cardiovascular Health and Diseases, Center for Cardiovascular Research, University of Cincinnati College of Medicine, Cincinnati, OH.
Childhood high blood pressure (BP) is linked to cardiovascular risk. This study identified novel molecular mechanisms, including Vasohibin-1 (VASH1) and Hyaluronidase1 (HYAL1) dysregulation, potentially mediating early cardiovascular target organ injury (CV-TOI) in hypertensive youth.
Area of Science:
- Cardiovascular Research
- Pediatric Hypertension
- Molecular Biology
Background:
- Childhood primary hypertension tracks into adulthood, increasing cardiovascular risk.
- Early cardiovascular target organ injury (CV-TOI) can be studied in youth, avoiding adult confounding factors.
Purpose of the Study:
- To explore molecular mechanisms of early CV-TOI in adolescents with high blood pressure (BP).
- To identify potential biomarkers and mediators of CV-TOI in hypertensive youth.
Main Methods:
- Stratified 132 youths by BP and left ventricular mass index (LVMI).
- Analyzed systemic circulating RNA, miRNA, methylation, and serum proteome profiles using high-throughput sequencing.
Main Results:
- Elevated VASH1 gene expression correlated with systolic BP.
- Downregulated hsa-miR-335-5p and upregulated PROZ/downregulated SOD3 observed in high-BP youths.
- Elevated HYAL1 levels identified in youths with high BP and high LVMI.
Conclusions:
- Findings suggest impaired angiogenesis and extracellular matrix degradation via VASH1 and HYAL1 dysregulation in hypertensive youth.
- Identified VASH1 and HYAL1 as potential mediators of CV-TOI, offering strategies for adult hypertension.
