Hepatocyte Growth Factor (HGF) Prevents the Apoptotic and Anti-Angiogenic Effect of Hypercholesterolemia on Hepatocytes in Liver Allografts
1Pathology, Baskent University, Ankara, Turkey, 2Department of General Surgery, Division of Transplantation, Baskent University, Ankara, Turkey
Meeting: 2020 American Transplant Congress
Abstract number: A-300
Keywords: Growth factors, Hepatocytes, Outcome
Session Information
Session Name: Poster Session A: Biomarkers, Immune Assessment and Clinical Outcomes
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Background: Hypercholesterolemia (HC) impairs angiogenesis and induces apoptosis in livers. This hyperlipidemic impairment of angiogenesis reported associated with reduced bFGF. HGF stimulates proliferation, angiogenesis, and plays a critical role in the regeneration process of the liver. HGF also acted as a metabolic regulator and increases in patients with hyperlipidemia. We evaluate whether HGF has a protective effect on hepatocytes of recipients with HC.
*Methods: Methods: Biopsies of 68 patients scored for steatosis, fibrosis, and inflammation. Angiogenesis highlighted with CD31 and apoptosis evaluated with the TUNNEL method. Expression of HGF, bFGF, TNF-α, and TGF-β evaluated by immunohistochemistry. Follow-up biopsies analyzed for the development of LF during 18 months after the initial biopsy.
*Results: Results: The degree of angiogenesis and bFGF decreases while the degree of apoptosis and macrophage increases with increasing level of cholesterol and triglycerides (p<0.001). Liver TGF-β and TNF-α expression found to increase with increasing serum cholesterol and triglycerides (p<0.01). The development of LF showed a significant correlation with the degree of mean cholesterol level, TGF-β, and TNF-α expression (P<0.001). HGF shows a significant correlation with the degree of angiogenesis and inverse correlation with apoptosis, macrophage infiltration, TGF-β, and TNF-α expression (p<0.001). The development of LF decreases with increasing expression of HGF (p<0.001). Of 30 patients with HC, 15 showed HGF expression (Group1) while remaining did not (Group2). The degree of angiogenesis found higher in Group1 than Group 2 (p<0.001).Group1 showed lower degree of apoptosis, TGF-β, TNF-α, and lower incidence of LF than Group2 (p<0.001). Mean graft survival was 39±6,3, 62±8,2, and 116±7 months for patients with negative, focal, and diffuse HGF expression, respectively (p<0.001).
*Conclusions: Conclusion: HGF is critical for organo-protection and liver regeneration under pathophysiological conditions. We suggest that HGF-based drugs show promise as part of a new arsenal in the fight to suppress allograft failure.
To cite this abstract in AMA style:
Ozdemir HB, Ozgun G, Polat AYucel, Haberal N, Moray G, Haberal M. Hepatocyte Growth Factor (HGF) Prevents the Apoptotic and Anti-Angiogenic Effect of Hypercholesterolemia on Hepatocytes in Liver Allografts [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/hepatocyte-growth-factor-hgf-prevents-the-apoptotic-and-anti-angiogenic-effect-of-hypercholesterolemia-on-hepatocytes-in-liver-allografts/. Accessed May 7, 2025.« Back to 2020 American Transplant Congress