Shiva Mohammadi,1,*Amir Shakarami,2
1. Department of Medical Biotechnology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran. 2. Department of Cardiology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
Introduction: CRISPR/Cas9 technology is a powerful technique that allows the generation of modified cells and organisms necessary to elucidate gene function and mechanisms in human diseases. CRISPR/Cas9 system has become one of the most popular approaches for genome editing in basic and clinical research because of its flexibility and simplicity. Cardiovascular disorder has been the emphasis of basic and clinical investigations because of its high incidence and high disability rate, immensely affecting patients' quality of life and long-term survival.
Methods: This study included peer-reviewed papers from Scopus, PubMed, Web of Science, and ScienceDirect databases from 2020 to 2023.
Results: CRISPR/Cas9 has increased the understanding of cardiovascular disorders (especially atherosclerosis and ischemia-reperfusion injury), lipid metabolism, and genetic inheritance. The pathogenic mechanism of atherosclerosis is intricate because several factors are involved in the pathogenesis. The lipid deposition process is the initial occurrence and expansion of atherosclerosis. Hyperlipidemia, particularly low-density lipoprotein cholesterol (LDL-C), has been revealed to be the most crucial trigger of atherosclerosis pathogenesis and the independent threat factor of cardiovascular disease. One of the most familiar pro-atherosclerotic genes is PCSK9 (pro-protein convertase subtilisin/kexin type9), a lipid metabolism-related gene. Intended disruption of PCSK9 activity through loss of function mutations can meaningfully decrease circulating LDL-C levels, prevent cardiomyocyte autophagy, and lower the danger of coronary heart disorder. Consequently, PCSK9 is one of the most concerned and likely targets of atherosclerosis gene therapy. CRISPR system is a hopeful way to knock down the PCSK9 gene in the human liver. Using CRISPR editors to knock down PCSK9 in cynomolgus monkeys, the CRISPR editors encouraged a considerable decrease in plasma PCSK9 level (90%) and, consequently, a higher decrease in plasma LDL-C level (60%).
Also, in ischemia-reperfusion injury, calcium calmodulin-dependent protein kinase IIδ (CaMKIIδ) is an essential protein. Targeting CaMKIIδ using CRISPR-Cas9 is a viable intervention to protect the heart tissue from ischemia-reperfusion damage in mouse models. Injecting gene editing reagents soon after ischemia exposure was sufficient for the mice to recover from severe heart damage.
Conclusion: This research showed CRISPR/Cas9 system could be a powerful tool in cardiovascular research and a new strategy for treating cardiovascular diseases.