Parkin-Dependent Mitophagy in Adipose Tissue promotes Aortic Aneurysm Growth
Presented During:
Monday, May 4, 2026: 9:00AM - 4:00PM
McCormick Place Lakeside Center
Posted Room Name:
Exhibit Hall, Poster Area
Abstract No:
P0147
Submission Type:
C. Walton Lillehei Resident Forum
Authors:
Ricky Patil (1), Matthew Kazaleh (1), Keyun Fu (1), Gorav Ailawadi (1), Morgan Salmon (2)
Institutions:
(1) University of Michigan Frankel Cardiovascular Center, Ann Arbor, MI, (2) N/A, Charlottesville, VA
Submitting Author:
Ricky Patil
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University of Michigan Frankel Cardiovascular Center
University of Michigan Frankel Cardiovascular Center
Co-Author(s):
Matthew Kazaleh
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University of Michigan Frankel Cardiovascular Center
University of Michigan Frankel Cardiovascular Center
Keyun Fu
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University of Michigan Frankel Cardiovascular Center
University of Michigan Frankel Cardiovascular Center
*Gorav Ailawadi
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University of Michigan Frankel Cardiovascular Center
University of Michigan Frankel Cardiovascular Center
Morgan Salmon
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Presenting Author:
Ricky Patil
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University of Michigan Frankel Cardiovascular Center
University of Michigan Frankel Cardiovascular Center
Abstract:
Objective: Inflammation in peri-vascular adipose tissue (PVAT) is known to contribute to aortic aneurysm (AA) pathogenesis. Mitophagy, the process of mitochondrial turnover, in PVAT may be a driver of disease progression. Parkin, an E3 Ubiquitin Ligase central to mitophagy, has already been identified as a driver of diet and age-induced adipogenesis in murine models. Thus, we investigated Parkin's role in PVAT inflammation and resultant AA phenotype.
Methods: Wild-type (WT) and Parkin knockout (PKO) mice underwent AA induction via laparotomy and topical elastase application to the abdominal aorta. AA size was measured at 14-days. Next, WT mice receiving WT fat transplant atop their aorta (WT-WT) and WT mice cross transplanted with PKO fat (WT-PKO) underwent elastase-induced AA generation. Similarly, PKO mice with transplanted PKO fat (PKO-PKO) and PKO mice cross transplanted with WT fat (PKO-WT) underwent AA induction. All experiments were conducted on both sexes. Murine white adipose tissue was utilized for all fat transplants.
Results: WT-WT fat transplanted mice demonstrated exaggerated AA growth compared to WT mice (male: 29.8% increase, p=0.008, female: 103.2% increase, p<0.0001) [Figure 1A]. However, WT-PKO mice, demonstrated attenuated growth compared to WT-WT mice (male: 94.6% decrease & female: 127.4% decrease, p<0.001 for both sexes) [Figure 1B & 1C].
In males, PKO-WT mice demonstrated decreased AA growth compared to PKO mice (males: 53.8% decrease, p=0.0317). Female PKO-WT mice demonstrated augmented AA size compared to PKO mice (females: 43.2% increase, p=0.1429). However, this cohort was affected by high mortality. Both male and female PKO-WT mice showed significantly higher mortality compared to PKO-PKO mice (male: PKO-WT: 40% [4/10] vs. PKO-PKO: 0% [0/10]) (female: PKO-WT: 67% [4/6] vs. PKO-PKO: 0% [0/8]) [p<0.01 for both]. By comparison, PKO-PKO mice all survived and demonstrated attenuated AA size compared to PKO-WT mice, regardless of recipient sex (males: 126.3% decrease p= 0.0081, female: 44.4% decrease, p= 0.0444) [Figure 1D & 1E].
Conclusion:
Silencing Parkin in transplanted fat attenuated AA growth compared to transplanted WT fat, regardless of recipient strain or sex. These findings suggest that Parkin mediated mitophagy may link perivascular adiposity with AA progression.
Methods: Wild-type (WT) and Parkin knockout (PKO) mice underwent AA induction via laparotomy and topical elastase application to the abdominal aorta. AA size was measured at 14-days. Next, WT mice receiving WT fat transplant atop their aorta (WT-WT) and WT mice cross transplanted with PKO fat (WT-PKO) underwent elastase-induced AA generation. Similarly, PKO mice with transplanted PKO fat (PKO-PKO) and PKO mice cross transplanted with WT fat (PKO-WT) underwent AA induction. All experiments were conducted on both sexes. Murine white adipose tissue was utilized for all fat transplants.
Results: WT-WT fat transplanted mice demonstrated exaggerated AA growth compared to WT mice (male: 29.8% increase, p=0.008, female: 103.2% increase, p<0.0001) [Figure 1A]. However, WT-PKO mice, demonstrated attenuated growth compared to WT-WT mice (male: 94.6% decrease & female: 127.4% decrease, p<0.001 for both sexes) [Figure 1B & 1C].
In males, PKO-WT mice demonstrated decreased AA growth compared to PKO mice (males: 53.8% decrease, p=0.0317). Female PKO-WT mice demonstrated augmented AA size compared to PKO mice (females: 43.2% increase, p=0.1429). However, this cohort was affected by high mortality. Both male and female PKO-WT mice showed significantly higher mortality compared to PKO-PKO mice (male: PKO-WT: 40% [4/10] vs. PKO-PKO: 0% [0/10]) (female: PKO-WT: 67% [4/6] vs. PKO-PKO: 0% [0/8]) [p<0.01 for both]. By comparison, PKO-PKO mice all survived and demonstrated attenuated AA size compared to PKO-WT mice, regardless of recipient sex (males: 126.3% decrease p= 0.0081, female: 44.4% decrease, p= 0.0444) [Figure 1D & 1E].
Conclusion:
Silencing Parkin in transplanted fat attenuated AA growth compared to transplanted WT fat, regardless of recipient strain or sex. These findings suggest that Parkin mediated mitophagy may link perivascular adiposity with AA progression.
Category:
Adult Cardiac
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