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Ventromedial Hypothalamus Activation Aggravates Hypertension Myocardial Remodeling Through the Sympathetic Nervous

Yuyang Zhou1,2,3,4, Zhihao Liu1,2,3,4, Zihan Liu1,2,3,4

  • 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Frontiers in Cardiovascular Medicine
|November 4, 2021
PubMed

Insights

Activating the ventromedial hypothalamus (VMH) in rats increased blood pressure and worsened cardiac remodeling. This may involve sympathetic nerve activation and the HIF-1α/PPARα/CPT-1 pathway, highlighting VMH

Area of Science:

  • Neuroscience
  • Cardiovascular Physiology
  • Molecular Biology

Background:

  • The ventromedial hypothalamus (VMH) plays a role in emotional stress responses, a known risk factor for cardiovascular diseases.
  • The specific involvement of the VMH in the development of cardiovascular diseases, particularly hypertension-related cardiac remodeling, remains largely unexplored.
  • Emotional stress impacts cardiovascular health, necessitating investigation into brain regions like the VMH.

Purpose of the Study:

  • To investigate the effects of VMH activation on hypertension-related cardiac remodeling in a rat model.
  • To elucidate the underlying molecular mechanisms by which VMH activation influences cardiovascular changes.
  • To explore the potential role of sympathetic nerve activation and specific signaling pathways in VMH-mediated effects.

Main Methods:

  • Rats underwent VMH injection with AAV-hSyn-hM3D(Gq) to enable chemogenetic activation.
  • Rats were divided into sham, hypertension (2K1C), and hypertension with VMH activation groups.
  • VMH activation was induced using clozapine-N-oxide, followed by assessment of blood pressure, cardiac remodeling, and molecular markers.

Main Results:

  • VMH activation significantly increased systolic blood pressure (SBP) and exacerbated cardiac remodeling in hypertensive rats.
  • Increased serum norepinephrine levels and sympathetic indices of heart rate variability were observed following VMH activation.
  • RNA sequencing and qPCR revealed VMH activation upregulated HIF-1α and downregulated PPARα and CPT-1, suggesting regulation of HIF-1 and PPAR signaling pathways and fatty acid metabolism.

Conclusions:

  • VMH activation exacerbates hypertension and cardiac remodeling, likely through increased sympathetic nerve activity.
  • The HIF-1α/PPARα/CPT-1 signaling pathway is implicated as a potential mechanism underlying these effects.
  • These findings identify the VMH as a critical node in the neuro-cardiovascular axis during hypertension.

Keywords:
CPT-1HIF-1αPPARαcardiac remodelinghypertensionsympathetic nervous systemventromedial hypothalamus

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