Related Experiment Video

Updated: Sep 9, 2025

Precision Ultrasound-guided Stem Cell Delivery for Vascular Repair in Aortic Diseases
04:59

Precision Ultrasound-guided Stem Cell Delivery for Vascular Repair in Aortic Diseases

Published on: June 20, 2025

300

Perivascular inflammation in the progression of aortic aneurysms in Marfan syndrome

Hiroyuki Sowa1, Hiroki Yagi1,2, Kazutaka Ueda1

  • 1Department of Cardiovascular Medicine, Graduate School of Medicine.

JCI Insight
|August 28, 2025
PubMed

Insights

Perivascular inflammation contributes to aortic dilatation in Marfan syndrome (MFS). Low-dose pitavastatin inhibited inflammation and aortic enlargement, suggesting it as a potential therapeutic target for MFS vascular events.

Area of Science:

  • Cardiovascular Biology
  • Inflammation Research
  • Genetics and Disease

Background:

  • Vascular diseases are significantly influenced by inflammation.
  • Marfan syndrome (MFS) is a genetic disorder affecting connective tissue, often leading to aortic dilatation.
  • The role of perivascular inflammation in MFS pathogenesis remains to be fully elucidated.

Purpose of the Study:

  • To investigate the involvement of perivascular inflammation in the aortic dilatation associated with Marfan syndrome.
  • To explore the therapeutic potential of pitavastatin in mitigating MFS-related vascular inflammation and pathology.
  • To develop a non-invasive method for assessing perivascular adipose tissue (PVAT) inflammation in MFS patients.

Main Methods:

  • Analysis of aortic tissues from MFS patients and Fbn1C1041G/+ mice for macrophage infiltration and inflammatory cytokine expression.
  • Induction of metabolic inflammatory stress using a high-fat diet (HFD) in Fbn1C1041G/+ mice, with and without pitavastatin treatment.
  • Histological and molecular analysis of aortic medial structural integrity, fibrosis, and TGF-β pathway activation.
  • Development and validation of a machine learning-based automated analysis program for CT images to calculate the ascending aorta perivascular fat attenuation index (AA-FAI).

Main Results:

  • MFS aorta and Fbn1C1041G/+ mouse aorta exhibited significant macrophage accumulation and increased inflammatory cytokines in periaortic tissues.
  • HFD exacerbated vascular inflammation and accelerated aortic dilatation in Fbn1C1041G/+ mice, effects inhibited by pitavastatin.
  • Pitavastatin treatment ameliorated HFD-induced structural disorganization, elastic fiber fragmentation, fibrosis, proteoglycan accumulation, and TGF-β pathway activation in the aorta.
  • The developed AA-FAI tool showed a significant correlation with periaortic fat inflammation and was elevated in MFS patients compared to controls.

Conclusions:

  • Perivascular inflammation is a key contributor to aneurysm formation in Marfan syndrome.
  • Targeting perivascular inflammation with agents like pitavastatin may offer a novel therapeutic strategy for MFS.
  • The AA-FAI serves as a promising non-invasive biomarker for assessing PVAT inflammation in clinical settings for MFS management.
Keywords:
CardiologyCardiovascular diseaseInflammation

More Related Videos

A New Murine Model of Endovascular Aortic Aneurysm Repair08:51

A New Murine Model of Endovascular Aortic Aneurysm Repair

Published on: July 7, 2013

14.5K
Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions06:08

Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions

Published on: March 8, 2019

19.7K

Related Concept Videos

Aneurysm I: Introduction01:30

Aneurysm I: Introduction

An aortic aneurysm is a localized outpouching or dilation at a weak point in the artery wall. It may involve different parts of the aorta, such as the abdominal aorta, aortic arch, or thoracic aorta.Etiological factorsSeveral disorders are associated with aortic aneurysms.Congenital causes, such as primary connective tissue disorders like Marfan syndrome, impact the integrity and strength of connective tissues, notably affecting the aorta. Marfan syndrome is a genetic disorder that specifically...
25
Aneurysm II: Clinical Manifestations and Diagnostic Studies01:21

Aneurysm II: Clinical Manifestations and Diagnostic Studies

Thoracic, aortic arch and abdominal aneurysms are significant vascular conditions that can present with various clinical manifestations and lead to serious complications. Understanding these manifestations and the appropriate diagnostic studies is essential for effective management and treatment.Thoracic Aortic AneurysmsThoracic aortic aneurysms often remain asymptomatic until they reach a size that impinges on adjacent structures. They typically cause deep, diffuse chest pain that radiates to...
21
Aortic Regurgitation I: Introduction01:15

Aortic Regurgitation I: Introduction

IntroductionAortic regurgitation is characterized by the backward flow of blood from the aorta into the left ventricle during diastole and arises from the improper closure of the aortic valve. This condition results in left ventricular volume overload and can stem from both acute and chronic etiologies, each contributing uniquely to the disease's progression and symptomatology.Acute and Chronic CausesAcute aortic regurgitation often results from events that suddenly impair the integrity of the...
36
Aneurysm III: Interprofessional Care01:26

Aneurysm III: Interprofessional Care

Aneurysm management involves either conservative medical therapy or surgical intervention, depending on the size and symptoms of the aneurysm. Conservative management is generally reserved for smaller, asymptomatic aneurysms, while larger or symptomatic aneurysms often necessitate surgical repair.Conservative Medical TherapyFor small, asymptomatic aneurysms, particularly abdominal aortic aneurysms (AAA) less than 5.5 centimeters in diameter, conservative medical therapy is recommended. This...
24
Peripheral Artery Disease I: Introduction01:30

Peripheral Artery Disease I: Introduction

Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty...
32
Mitral Valve Prolapse I: Introduction01:27

Mitral Valve Prolapse I: Introduction

IntroductionThe mitral valve, one of the heart's four valves, regulates blood flow. These valves have flaps that open and close to direct blood properly through the heart and body. During each heartbeat, the flaps open for blood to pass through and seal shut to prevent backflow. Specifically, the mitral valve opens to allow blood flow from the heart's upper left chamber to the lower left chamber. It then closes securely as the lower left chamber contracts to pump blood to the body, preventing...
42