Macrophage depletion lowers blood pressure and reduces renal fibrosis progression in existing hypertension mice model

TL;DR

Removing macrophages in mice with existing high blood pressure lowers their blood pressure and slows kidney damage, suggesting macrophages could be a new treatment target.

Contribution

This study shows macrophage depletion reduces blood pressure and fibrosis in pre-existing hypertension, a novel therapeutic approach.

Findings

Macrophage depletion reduced blood pressure in hypertensive mice.

Renal fibrosis markers like Col1a1 and Acta2 decreased after macrophage depletion.

Renal macrophage infiltration and fibrosis start early in hypertension development.

Abstract

Uncontrolled hypertension is a global health issue with 40 % of hypertensive patients not achieving blood pressure control with current therapies. Previously, we demonstrated renal macrophage infiltration during hypertension development with macrophage depletion leading to reduced blood pressure and renal fibrosis. However, the effect of macrophage depletion in existing hypertension has not been evaluated. We induced hypertension in mice then depleted macrophages and assessed blood pressure and renal fibrosis. Separately induced hypertension and assessed renal macrophage population and fibrosis early in hypertension. Results showed increased renal macrophage, Acta2 early in hypertension development. Macrophage depletion led to reduced blood pressure in the hypertensive mice, decreased kidney Col1a1, Acta2, Col3a1 and Fn1. This study shows that renal macrophage infiltration and fibrosis begin early in hypertension development and depleting macrophages in hypertension reduces blood pressure and suppress renal fibrosis. This shows macrophages are a potential target in treatment of hypertension.

•Macrophage depletion lowers blood pressure in pre-existing hypertension.•Renal macrophages infiltrate early in hypertension development.•Macrophage depletion reduces kidney fibrosis progression in hypertension.•Renal fibrosis begins in the early stages of hypertension.•Targeting macrophages may offer new hypertension treatments.

Macrophage depletion lowers blood pressure in pre-existing hypertension.

Renal macrophages infiltrate early in hypertension development.

Macrophage depletion reduces kidney fibrosis progression in hypertension.

Renal fibrosis begins in the early stages of hypertension.

Targeting macrophages may offer new hypertension treatments.

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