Mohammadi Abbas, Karimian Azin, Shokri Kasra, Mohammadi Ashkan, Hazhir-Karzar Nazanin, Bahar Rayeheh, Radfar Azar, Pakyari Mohammadreza, Tehrani Behnam
Department of Internal Medicine, Valley Health System, Las Vegas, NV, USA.
Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
J Cardiovasc Transl Res. 2025 Mar 13. doi: 10.1007/s12265-025-10603-4.
Cardio-Kidney-Metabolic (CKM) Syndrome involves metabolic, kidney, and cardiovascular dysfunction, disproportionately affecting disadvantaged groups. Its staging (0-4) highlights the importance of early intervention. While current management targets hypertension, heart failure, dyslipidemia, and diabetes, RNA-based therapies offer innovative solutions by addressing molecular mechanisms of CKM Syndrome. Emerging RNA treatments, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), show promise in slowing disease progression across CKM stages. For example, ASOs and siRNAs targeting ApoC-III and ANGPTL3 reduce triglycerides and LDL cholesterol, while siRNAs improve blood pressure control by targeting the renin-angiotensin-aldosterone system. Obesity treatments leveraging miRNAs and circRNAs tackle a key CKM risk factor. In heart failure and diabetes, RNA-based therapies improve cardiac function and glucose control, while early kidney disease trials show potential for RNAi in acute injury. Further research is essential to refine these therapies and ensure equitable access.
心肾代谢（CKM）综合征涉及代谢、肾脏和心血管功能障碍，对弱势群体的影响尤为严重。其分期（0-4期）凸显了早期干预的重要性。虽然目前的治疗针对高血压、心力衰竭、血脂异常和糖尿病，但基于RNA的疗法通过解决CKM综合征的分子机制提供了创新的解决方案。新兴的RNA治疗方法，包括反义寡核苷酸（ASO）和小干扰RNA（siRNA），在减缓CKM综合征各阶段疾病进展方面显示出前景。例如，靶向载脂蛋白C-III（ApoC-III）和血管生成素样蛋白3（ANGPTL3）的ASO和siRNA可降低甘油三酯和低密度脂蛋白胆固醇，而siRNA通过靶向肾素-血管紧张素-醛固酮系统改善血压控制。利用微小RNA（miRNA）和环状RNA（circRNA）的肥胖治疗方法解决了CKM的一个关键危险因素。在心力衰竭和糖尿病中，基于RNA的疗法可改善心脏功能和血糖控制，而早期肾脏疾病试验显示RNA干扰在急性损伤中有潜力。进一步的研究对于优化这些疗法并确保公平可及性至关重要。
