Age and Metabolic Syndrome-dependent acceleration of coronary artery disease in miniature Ossabaw swine

Background: Coronary artery disease (CAD) remains a leading global cause of mortality, with over 375,000 deaths in the United States in 2021. Atherosclerosis is central to CAD progression and is effectively modeled in miniature Ossabaw swine, which naturally develop metabolic and cardiovascular abnormalities resembling human disease. Aging and metabolic syndrome (MetS) are known to influence cholesterol, glucose regulation, cardiac stress markers, systemic blood pressure, and body weight – all factors associated with increased CAD risk. We hypothesized that MetS would elicit greater atherosclerosis than aging alone. Methods: Ossabaw swine were assigned to young lean (1.2 y, n=7), old lean (12.5 y, n=7), and young MetS diet (2.3 y, n=3) groups. Intravascular ultrasound imaging was performed in the left anterior descending (LAD) artery. LAD pullbacks at 1 mm/s were used to evaluate vascular morphology and atherosclerotic burden. Complete blood count, chemistry, aortic and left ventricular blood pressures were collected to assess metabolic and cardiovascular status. Results: Young MetS showed 6-fold increase in total cholesterol and 1.4-fold increase in fasting glucose, while young and old lean pigs remained near normal ranges. Body weight (kg) increased with both age and metabolic status: young lean (34±1.6), old lean (71±7.1), and young MetS (73±0.88). Similar patterns were observed in central hemodynamics. Left ventricular pressure: young lean (131/3 mmHg), old lean (123/8 mmHg), and young MetS (164/0 mmHg). Aortic pressures followed the same trend: young lean (125/90 mmHg, old lean (130/93 mmHg), and young MetS (147/113 mmHg). LAD plaque burden: young lean (1%), old lean (35%), and young MetS (37%). Discussion: Lean Ossabaw miniature swine develop CAD as they age, despite having a relatively normal metabolic status, demonstrating that aging alone is sufficient to permit atherosclerosis. Even though both lean groups had relatively normal plasma cholesterol levels, only the old lean pigs developed CAD, suggesting a cumulative effect of lifetime cholesterol exposure on disease progression; alternatively, age-related cellular senescence may represent an independent pro-atherogenic mechanism. While aging is a factor contributing to CAD development, MetS had a greater effect on metabolic dysfunction, hypertension, and atherosclerotic burden over a profoundly shorter time course. Conclusion: Aging is an enabler of CAD development and MetS dramatically accelerates its onset and severity. Support: CorVus Foundation, Inc This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.