Figure 1.
Molecular mechanisms of fibroblast activation and fibrosis in hypertension. Hypertension induces pressure overload, left ventricular (LV) hypertrophy, and fibrosis through activation of fibrotic signaling in fibroblasts. Release of angiotensin II (ANG II) in hypertension releases growth factors like transforming growth factor β (TGFβ), connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI1), and endothelin 1 (ET1), which can induce fibrotic gene through Smad phosphorylation and activation. TGFβ and other stimuli can also induce fibrosis through mitogen-activated protein kinase (MAPK) signaling. Angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), piperine/leflunomide, and peroxisome proliferator receptor (PPAR)-γ can block fibrotic signaling by acting at various target points. AT1R, AT1 receptor; ECM, extracellular matrix; RhoA, Ras homolog family member A. Images created with a licensed version of BioRender.com.