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Volume 25
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10.3390/ijms252312782
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Article

Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis

by
Ishita Kathuria
1,
Aditi Prasad
1,
Bal Krishan Sharma
2,
Ravi Varma Aithabathula
1,
Malvin Ofosu-Boateng
1,
Maxwell A. Gyamfi
1,
Jianxiong Jiang
1,
Frank Park
1,
Udai P. Singh
1 and
Bhupesh Singla
1,*
1
Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38103, USA
2
Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(23), 12782; https://doi.org/10.3390/ijms252312782
Submission received: 26 October 2024 / Revised: 22 November 2024 / Accepted: 26 November 2024 / Published: 28 November 2024
(This article belongs to the Special Issue Atherosclerosis 2.0: From Molecular Mechanisms, Pathophysiology to Novel Therapeutic Approaches)
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Abstract

Clinical and genetic studies strongly support a significant connection between nonalcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD) and identify ASCVD as the primary cause of death in NAFLD patients. Understanding the molecular factors and mechanisms regulating these diseases is critical for developing novel therapies that target them simultaneously. Our preliminary immunoblotting experiments demonstrated elevated expression of nidogen 2 (NID2), a basement membrane glycoprotein, in human atherosclerotic vascular tissues and murine steatotic livers. Therefore, we investigated the role of NID2 in regulating hepatosteatosis and atherosclerosis utilizing Western diet-fed Apoe−/− mice with/without NID2 overexpression. Quantitative real-time PCR confirmed increased NID2 mRNA expression in multiple organs (liver, heart, kidney, and adipose) of NID2-overexpressing mice. Male mice with NID2 overexpression exhibited higher liver and epididymal white adipose tissue mass, increased hepatic lipid accumulation, and fibrosis. Additionally, these mice developed larger atherosclerotic lesions in the whole aortas and aortic roots, with increased necrotic core formation. Mechanistic studies showed reduced AMPK activation in the livers of NID2-overexpressing mice compared with controls, without any effects on hepatic inflammation. In conclusion, these findings suggest that NID2 plays a deleterious role in both hepatosteatosis and atherosclerosis, making it a potential therapeutic target for these conditions.
Keywords: nidogen 2; hepatosteatosis; atherosclerosis; AMPK; NAFLD nidogen 2; hepatosteatosis; atherosclerosis; AMPK; NAFLD

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MDPI and ACS Style

Kathuria, I.; Prasad, A.; Sharma, B.K.; Aithabathula, R.V.; Ofosu-Boateng, M.; Gyamfi, M.A.; Jiang, J.; Park, F.; Singh, U.P.; Singla, B. Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis. Int. J. Mol. Sci. 2024, 25, 12782. https://doi.org/10.3390/ijms252312782

AMA Style

Kathuria I, Prasad A, Sharma BK, Aithabathula RV, Ofosu-Boateng M, Gyamfi MA, Jiang J, Park F, Singh UP, Singla B. Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis. International Journal of Molecular Sciences. 2024; 25(23):12782. https://doi.org/10.3390/ijms252312782

Chicago/Turabian Style

Kathuria, Ishita, Aditi Prasad, Bal Krishan Sharma, Ravi Varma Aithabathula, Malvin Ofosu-Boateng, Maxwell A. Gyamfi, Jianxiong Jiang, Frank Park, Udai P. Singh, and Bhupesh Singla. 2024. "Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis" International Journal of Molecular Sciences 25, no. 23: 12782. https://doi.org/10.3390/ijms252312782

APA Style

Kathuria, I., Prasad, A., Sharma, B. K., Aithabathula, R. V., Ofosu-Boateng, M., Gyamfi, M. A., Jiang, J., Park, F., Singh, U. P., & Singla, B. (2024). Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis. International Journal of Molecular Sciences, 25(23), 12782. https://doi.org/10.3390/ijms252312782

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