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Knockdown of CXCL13 Improves Vascular Remodeling, Reduces Blood Pressure and Protects the Heart in a Hypertensive rat
Jie Ma1, Xiaoguang Sun1, Xianjun Hu1
1Department of Cardiovascular Medicine, Chaohu Hospital affiliated to Anhui Medical University, Hefei, China.
Insights
Reducing Chemokine (CXC motif) ligand 13 (CXCL13) levels improved blood pressure and protected the heart in a hypertension model. This suggests CXCL13 influences hypertension via the PF4V1/NF-κB pathway.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Hypertension Research
Background:
- Cardiovascular disease is a leading global cause of death, with hypertension as a major risk factor.
- Chemokine (CXC motif) ligand 13 (CXCL13) is implicated in disease development and angiogenesis.
- The role of CXCL13 in hypertension and its regulatory mechanisms remain largely unexplored.
Purpose of the Study:
- To investigate the impact of CXCL13 on hypertension.
- To elucidate the underlying regulatory mechanisms of CXCL13 in hypertension.
- To explore potential therapeutic strategies targeting CXCL13 for hypertension.
Main Methods:
- Established a rat model of hypertension induced by Angiotensin II (Ang II) treatment.
- Quantified protein and mRNA expression of CXCL13 using Western blot and RT-qPCR.
- Assessed systolic blood pressure, ET-1 levels, vascular remodeling, and cardiac biomarkers (ACE, TBARS, BNP).
Main Results:
- CXCL13 expression was significantly elevated in the hypertensive rat model.
- Knockdown of CXCL13 improved vascular remodeling and reduced blood pressure.
- Suppression of CXCL13 protected the heart by decreasing ACE, TBARS, and BNP levels.
- CXCL13 was found to modulate the PF4V1/NF-κB pathway, with PF4V1 being crucial for CXCL13's effect on hypertension.
Conclusions:
- Downregulation of CXCL13 ameliorates hypertension by improving vascular remodeling and protecting the heart.
- The PF4V1/NF-κB signaling pathway is a key mechanism through which CXCL13 influences hypertension.
- Targeting CXCL13 presents a potential novel therapeutic approach for managing hypertension.
Abstract:
BackgroundCardiovascular disease remains the first major reason for death in global, and hypertension is one very usual risk factor for this disease. Chemokine (CXC motif) ligand 13 (CXCL13) exhibits a crucial role in the development and angiogenesis of a variety of diseases. However, the impacts of CXCL13 in the amelioration of hypertension and the associated regulatory mechanisms have rarely reported.MethodsThe hypertensive rat model was induced by Ang II treatment. The protein and mRNA expressions were measured through western blot and RT-qPCR. The systolic blood pressure was monitored. The ET-1 level was examined through the commercial kit. The thickness of vascular elasticity layer was observed through hematoxylin eosin staining. The levels of angiotensin-converting enzyme (ACE), thiobarbituric acid-reactive substances (TBARS), and brain natriuretic peptide (BNP) were inspected through the commercial kits.ResultsCXCL13 exhibited high protein and mRNA expressions in hypertensive rat model. Knockdown of CXCL13 improved vascular remodeling and elevated blood pressure in hypertensive rat model. Moreover, suppression of CXCL13 protected heart in hypertensive rat model through declining the levels of ACE, TBARS, and serum BNP. Next, it was demonstrated that CXCL13 modulated the PF4V1/NF-κB pathway. Eventually, through rescue assays, it was proved that CXCL13 ameliorated hypertension through affecting PF4V1.ConclusionThis study manifested that knockdown of CXCL13 improved vascular remodeling, reduced blood pressure, and protected the heart by affecting the PF4V1/NF-κB signaling pathway in a hypertensive rat model. This discovery may offer novel opinions in the treatment of hypertension.
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