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RNA Therapies in Cardio-Kidney-Metabolic Syndrome: Advancing Disease Management

Abbas Mohammadi1, Azin Karimian2, Kasra Shokri2

  • 1Department of Internal Medicine, Valley Health System, Las Vegas, NV, USA. abbas_pr2005@hotmail.com.

Journal of Cardiovascular Translational Research
|March 13, 2025
PubMed

Insights

Cardio-Kidney-Metabolic (CKM) Syndrome, affecting vulnerable populations, can be managed with novel RNA-based therapies. These treatments target molecular pathways to slow disease progression and improve patient outcomes.

Area of Science:

  • Biochemistry
  • Genetics
  • Pharmacology

Background:

  • Cardio-Kidney-Metabolic (CKM) Syndrome integrates metabolic, renal, and cardiovascular dysfunctions, with a notable impact on underserved communities.
  • The syndrome's 0-4 staging underscores the critical need for early therapeutic interventions.
  • Current treatments focus on managing hypertension, heart failure, dyslipidemia, and diabetes.

Purpose of the Study:

  • To explore the potential of RNA-based therapies in addressing the molecular underpinnings of CKM Syndrome.
  • To evaluate emerging RNA treatments, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), for CKM Syndrome management.
  • To assess the efficacy of RNA therapeutics in improving cardiovascular, kidney, and metabolic parameters in CKM Syndrome.

Main Methods:

  • Investigating ASOs and siRNAs targeting ApoC-III and ANGPTL3 to modulate lipid profiles.
  • Examining siRNAs for blood pressure regulation via the renin-angiotensin-aldosterone system.
  • Exploring microRNAs (miRNAs) and circular RNAs (circRNAs) for obesity management.
  • Reviewing RNA-based interventions for heart failure, diabetes, and acute kidney injury.

Main Results:

  • ASOs and siRNAs targeting ApoC-III and ANGPTL3 demonstrated reductions in triglycerides and LDL cholesterol.
  • siRNA interventions showed promise in enhancing blood pressure control.
  • miRNAs and circRNAs offer potential strategies for tackling obesity, a key CKM risk factor.
  • RNA-based therapies exhibited improvements in cardiac function and glycemic control in heart failure and diabetes models.
  • Early trials suggest RNA interference (RNAi) efficacy in mitigating acute kidney injury.

Conclusions:

  • RNA-based therapies, including ASOs, siRNAs, miRNAs, and circRNAs, represent a promising frontier for CKM Syndrome treatment.
  • These novel approaches target core molecular mechanisms, offering potential to slow disease progression across all CKM stages.
  • Further research and equitable access are crucial for realizing the full therapeutic potential of RNA-based interventions in CKM Syndrome.

Keywords:
Cardio-Kidney-Metabolic (CKM) SyndromeClinical trialsRNA-based therapiesTranslational medicine

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