Jana Hua-Monclús was peering through a microscope in a Barcelona lab when her team uncovered something unexpected: the fat hugging the aorta isn’t just padding—it’s a quiet regulator of vascular health in Marfan syndrome. Led by Francesc Jiménez-Altayo at the Universitat Autònoma de Barcelona (UAB) and the CIBERCV cardiovascular research network, a study using murine models has revealed that perivascular adipose tissue (PVAT)—long thought to be inert—actively modulates aortic function in Marfan syndrome, with effects that shift dramatically by anatomical region and sex. This discovery, published in Biochemical Pharmacology (2026), reframes how scientists understand the disease’s progression and opens new pathways for targeted therapies.
Marfan syndrome, affecting about 1 in 5,000 people worldwide, stems from mutations in the fibrillin-1 gene and weakens connective tissues throughout the body. Its most life-threatening consequences involve the aorta, where progressive dilation can lead to dissection or rupture. While the condition strikes men and women equally, clinical outcomes differ—women often experience later onset of severe complications, a pattern now potentially explained by the newly discovered role of PVAT. The Barcelona team analyzed aortic responses in male and female Marfan mice across different ages, focusing on how surrounding fat influences vascular contraction.
The findings were striking: in female Marfan mice, PVAT significantly reduced the contractile force of the ascending aorta—a protective anticontractile effect linked to redox (oxidative balance) mechanisms. This effect vanished with age, suggesting a time-limited window of metabolic protection. Crucially, the modulation occurred independently of the endothelium, the blood vessel’s inner lining, pointing to a previously unrecognized signaling pathway between fat and vascular muscle. In contrast, male mice showed no such PVAT-mediated relaxation, underscoring the sex-specific nature of the response. The anatomical specificity was equally clear—effects in the ascending aorta were not mirrored in other aortic segments.
“The findings suggest that the immediate environment of the aorta is not a mere anatomical companion, but a dynamic element capable of influencing the evolution of the disease,” says Jiménez-Altayo. This shift in perspective—from passive fat to active regulator—could transform treatment strategies. Instead of focusing solely on the aortic wall, future therapies might target the metabolic crosstalk between PVAT and vascular tissue, especially in early-stage female patients. The study also involved researchers from CIBERNED and international institutions, highlighting the collaborative push to decode complex disease mechanisms.
As precision medicine advances, this work underscores the need to consider sex, age, and regional anatomy in both research and treatment. What was once dismissed as biological filler is now emerging as a key player in vascular resilience—offering hope for more nuanced, effective care for Marfan patients in the years ahead.