Longitudinal multi-organ transcriptomic atlas of salt-induced hypertension

Ratnakar Tiwari; Olha Kravtsova; Lashodya V. Dissanayake; Melissa Lowe; Biyang Xu; Vladislav Levchenko; Steven Didik; Ruslan Bohovyk; Daria V. Ilatovskaya; Oleg Palygin; Alexander Staruschenko

doi:10.1172/jci.insight.200841

Longitudinal multi-organ transcriptomic atlas of salt-induced hypertension

Ratnakar Tiwari,¹ Olha Kravtsova,¹ Lashodya V. Dissanayake,¹ Melissa Lowe,¹ Biyang Xu,¹ Vladislav Levchenko,¹ Steven Didik,¹ Ruslan Bohovyk,¹ Daria V. Ilatovskaya,² Oleg Palygin,³ and Alexander Staruschenko¹

Published April 23, 2026 - More info

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Abstract

High dietary salt intake elevates blood pressure and drives multi-organ damage. However, the molecular programs underlying progressive organ injury remain poorly defined. Here, we present a longitudinal multi-organ transcriptomic atlas of salt-induced hypertensive injury. We profiled kidney cortex, kidney medulla, heart, and liver across four stages spanning early hypertension to advanced pathology in Dahl salt-sensitive rats. We identified dynamic and tissue-specific molecular trajectories, including a shared early proliferative response that converges on proinflammatory and fibrotic remodeling. Notably, we uncovered compartment-specific renal responses, showing that the cortex and medulla, despite their proximity, follow distinct molecular trajectories during disease progression. We further identified 79 stage- and tissue-specific transcription factors that drive gene expression dynamics in salt-induced hypertensive injury. Integration with human genome-wide association studies revealed conserved pathways in endocrine signaling, ion transport, lipid metabolism, and detoxification, establishing cross-species relevance and highlighting mechanistic targets of clinical importance. Compound–transcriptome analysis revealed stage- and organ-specific therapeutic opportunities, prioritizing kinase and epigenetic modulators as candidates to rebalance maladaptive gene programs. Overall, this study provides a resource for understanding molecular mechanisms from early salt-induced hypertension to tissue-specific injury and underscores the need for precision interventions.

Longitudinal multi-organ transcriptomic atlas of salt-induced hypertension

Ratnakar Tiwari,¹ Olha Kravtsova,¹ Lashodya V. Dissanayake,¹ Melissa Lowe,¹ Biyang Xu,¹ Vladislav Levchenko,¹ Steven Didik,¹ Ruslan Bohovyk,¹ Daria V. Ilatovskaya,² Oleg Palygin,³ and Alexander Staruschenko¹

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Longitudinal multi-organ transcriptomic atlas of salt-induced hypertension

Ratnakar Tiwari,1 Olha Kravtsova,1 Lashodya V. Dissanayake,1 Melissa Lowe,1 Biyang Xu,1 Vladislav Levchenko,1 Steven Didik,1 Ruslan Bohovyk,1 Daria V. Ilatovskaya,2 Oleg Palygin,3 and Alexander Staruschenko1

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Ratnakar Tiwari,¹ Olha Kravtsova,¹ Lashodya V. Dissanayake,¹ Melissa Lowe,¹ Biyang Xu,¹ Vladislav Levchenko,¹ Steven Didik,¹ Ruslan Bohovyk,¹ Daria V. Ilatovskaya,² Oleg Palygin,³ and Alexander Staruschenko¹