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Mitophagy in Hypertensive Cardiac Hypertrophy: Mechanisms and Therapeutic Implications

Shijun Li1, Xiaoying Li1

  • 1Department of Hainan Health Care, The Second Medical Center of Chinese PLA General Hospital at Haitang Bay, Sanya, Hainan, PR China.

Journal of Clinical Hypertension (Greenwich, Conn.)
|August 18, 2025
PubMed

Insights

Mitophagy, a process removing damaged mitochondria, plays a dual role in hypertensive cardiac hypertrophy (HCH). Its dysregulation contributes to heart failure, but targeted modulation offers therapeutic potential for HCH.

Area of Science:

  • Cardiovascular Biology
  • Mitochondrial Biology
  • Cellular Autophagy

Background:

  • Hypertensive cardiac hypertrophy (HCH) is a maladaptive response to chronic pressure overload, often leading to heart failure.
  • Mitochondrial dysfunction is a key driver of HCH pathogenesis.
  • Impaired mitophagy, the selective removal of damaged mitochondria, contributes to cardiomyocyte death, oxidative stress, and fibrosis in HCH.

Purpose of the Study:

  • To review the molecular mechanisms of mitophagy dysregulation in HCH.
  • To explore the dual role of mitophagy (protective vs. detrimental) in HCH progression.
  • To discuss potential therapeutic strategies targeting mitophagy for HCH treatment.

Main Methods:

  • Comprehensive literature review of mitophagy pathways in HCH.
  • Analysis of key molecular players including PINK1/Parkin, BNIP3/NIX, and FUNDC1.
  • Examination of the interplay between mitophagy and mitochondrial biogenesis, inflammasome activation, and metabolic remodeling.

Main Results:

  • Mitophagy dysregulation, either insufficient or excessive, exacerbates mitochondrial dysfunction in HCH.
  • Dysfunctional mitophagy drives pathological hypertrophy, fibrosis, and bioenergetic crisis.
  • Understanding mitophagy's context-dependent role is crucial for therapeutic intervention.

Conclusions:

  • Mitophagy's dual nature in HCH presents a therapeutic paradox requiring precise modulation.
  • Targeting mitophagy pathways offers promising avenues for novel precision medicine strategies in cardiovascular disease.
  • Further research into mitophagy regulation may lead to effective treatments for HCH and heart failure.

Keywords:
hypertensive cardiac hypertrophymitochondrial dysfunctionmitophagyoxidative stresstherapeutic targets

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