Olalekan Samuel Oluwadare, Bakare Olalekan Olanrewaju, Okwute Patrick Godwin, Osonuga Ifabunmi Oduyemi, Adeyanju Muinat Moronke, Edema Victoria Biola
Department of Physiology, Faculty of Basic Medical Sciences, Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University, Sagamu Campus, Sagamu, Ogun State, Nigeria.
Department of Biochemistry, Olabisi Onabanjo University, Sagamu Campus, Sagamu, Ogun State, Nigeria.
Egypt Heart J. 2025 Jan 7;77(1):5. doi: 10.1186/s43044-024-00600-4.
Hypertrophic cardiomyopathy (HCM) is a frequently encountered cardiac condition worldwide, often inherited, and characterized by intricate phenotypic and genetic manifestations. The natural progression of HCM is diverse, largely due to mutations in the contractile and relaxation proteins of the heart. These mutations disrupt the normal structure and functioning of the heart muscle, particularly affecting genes that encode proteins involved in the contraction and relaxation of cardiac muscle.
This review focused on understanding the role of contractile and relaxation proteins in the pathogenesis of hypertrophic cardiomyopathy. Mutations in contractile proteins such as myosin, actin, tropomyosin, and troponin are associated with hypercontractility and increased sensitivity of the heart muscle, leading to HCM. Additionally, impaired relaxation of the heart muscle, linked to abnormalities in proteins like phospholamban, sarcolipin, titin, myosin binding protein-C, and calsequestrin, contributes significantly to the disease. The review also explored the impact of targeted therapeutic approaches aimed at modulating these proteins to improve patient outcomes. Recent advances in therapeutic strategies, including novel pharmacological agents like mavacamten and aficamten, were examined for their potential to help patients manage the disease and lead more accommodating lifestyles.
The review underscored the significance of early diagnosis and personalized treatment approaches in managing HCM. Future research should prioritize the development of robust biomarkers for early detection and risk stratification, particularly in diverse populations, to enhance clinical outcomes. Furthermore, it is imperative to delve deeper into the genetic mutations and molecular mechanisms associated with HCM, with a focus on exploring the roles of less-studied myocardial relaxation proteins and their interactions with sarcomere constituents.
肥厚型心肌病（HCM）是一种在全球范围内常见的心脏疾病，通常具有遗传性，其特征为复杂的表型和基因表现。HCM的自然病程多种多样，主要是由于心脏收缩和舒张蛋白的突变。这些突变破坏了心肌的正常结构和功能，尤其影响编码参与心肌收缩和舒张的蛋白质的基因。
本综述着重于理解收缩和舒张蛋白在肥厚型心肌病发病机制中的作用。肌球蛋白、肌动蛋白、原肌球蛋白和肌钙蛋白等收缩蛋白的突变与心肌的过度收缩和敏感性增加有关，从而导致HCM。此外，心肌舒张功能受损与受磷蛋白、肌浆蛋白、肌联蛋白、肌球蛋白结合蛋白-C和肌钙网蛋白等蛋白质异常有关，这对该疾病有显著影响。该综述还探讨了旨在调节这些蛋白质以改善患者预后的靶向治疗方法的影响。研究了治疗策略的最新进展，包括像mavacamten和aficamten等新型药物制剂，以评估它们帮助患者控制疾病并过上更适应生活方式的潜力。
该综述强调了早期诊断和个性化治疗方法在管理HCM中的重要性。未来的研究应优先开发用于早期检测和风险分层的强大生物标志物，特别是在不同人群中，以改善临床结果。此外，必须更深入地研究与HCM相关的基因突变和分子机制，重点是探索研究较少的心肌舒张蛋白的作用及其与肌节成分的相互作用。
