Transcriptomic Signatures of Vascular Smooth Muscle Cell Phenotypic Switching in Hypertensive End-Organ Damage: A Systems Physiology Investigation in South West Nigerian Patients

Background: Vascular smooth muscle cell phenotypic switching from a contractile to a synthetic state is a fundamental mechanism underlying hypertensive vascular remodelling, arterial stiffening, and end-organ damage. Transcriptomic drivers of this switching, including smooth muscle alpha-actin, osteopontin, and matrix metalloproteinase gene networks, have been characterised predominantly in non-African populations. Nigerian hypertensive patients exhibit earlier and more severe end-organ damage at equivalent blood pressure levels than European counterparts, suggesting population-specific pathophysiology. Objectives: This study aims to perform RNA sequencing on saphenous vein smooth muscle cells cultured from hypertensive patients with and without end-organ damage and from normotensive controls recruited at the University College Hospital Ibadan, to identify differentially expressed gene networks regulating phenotypic switching, and to validate top candidates by quantitative RT-PCR, western blot, and immunofluorescence in patient-derived aortic biopsy tissue. Methods: Saphenous vein segments will be obtained from thirty hypertensives with end-organ damage, thirty hypertensives without end-organ damage, and twenty normotensive controls undergoing elective cardiovascular surgery. Smooth muscle cells will be cultured and stimulated with angiotensin II. RNA sequencing will be performed using Illumina NovaSeq. Differential expression analysis will use DESeq2 with gene set enrichment analysis. Aortic tissue will be collected concurrently for validation immunostaining. Expected Outcomes: Hypertensive end-organ damage patients are hypothesised to exhibit upregulated osteopontin and matrix metalloproteinase-9 networks with suppressed contractile gene expression, forming a pro-remodelling transcriptomic signature distinct from non-African reference datasets. Conclusion: This study will produce original transcriptomic vascular physiology data with direct relevance to understanding hypertensive end-organ damage mechanisms in Yoruba and broader Nigerian populations. Keywords: vascular smooth muscle, phenotypic switching, RNA sequencing, hypertensive remodelling, Ibadan.