The ascending aorta of male hypertensive bicuspid aortic valve patients preferentially associated with a cellular aneurysmal phenotype

Bergeron, Alexandre; Hertig, Vanessa; Villeneuve, Louis; Chauvette, Vincent; El-Hamamsy, Ismaı̈l; Calderone, Angelino

doi:10.14814/phy2.15251

Cited by 3 publications

(2 citation statements)

References 52 publications

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“…The results about sex disparity of MMP-2 in CVDs are conflicting and at variance with the considered condition. For instance, male patients affected by aneurysms have shown increased levels of MMP-2 in the aorta [ 90 ], a fact confirmed also in vivo in the mouse model [ 91 ] and in vitro on rat smooth muscle cells [ 92 ]. However, the opposite was found in females when considering patients with bicuspid valve thoracic aortic aneurysm (BV-AAA) [ 93 , 94 ].…”

Section: Sex Differences In Mmps and Pathologiesmentioning

confidence: 85%

“…MMP-9 is far, together with MMP-2, the most studied metalloprotease in all aspects of CVDs, especially considering its connection with inflammation [ 105 ]. Most of the studies present in the literature have found an increase in the ascending aorta of male patients affected by aneurysms [ 90 , 93 , 106 ], with only one report finding the opposite result in females [ 91 ]. The former results are in large agreement with the clinical observation of a higher prevalence of aneurysms in males, making it a striking example of male disadvantage in CVDs [ 104 ].…”

Section: Sex Differences In Mmps and Pathologiesmentioning

confidence: 99%

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Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases

Trentini

Manfrinato

Castellazzi

et al. 2022

JPM

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It is now established that sex differences occur in clinical manifestation, disease progression, and prognosis for both cardiovascular (CVDs) and central nervous system (CNS) disorders. As such, a great deal of effort is now being put into understanding these differences and turning them into “advantages”: (a) for the discovery of new sex-specific biomarkers and (b) through a review of old biomarkers from the perspective of the “newly” discovered sex/gender medicine. This is also true for matrix metalloproteinases (MMPs), enzymes involved in extracellular matrix (ECM) remodelling, which play a role in both CVDs and CNS disorders. However, most of the studies conducted up to now relegated sex to a mere confounding variable used for statistical model correction rather than a determining factor that can influence MMP levels and, in turn, disease prognosis. Consistently, this approach causes a loss of information that might help clinicians in identifying novel patterns and improve the applicability of MMPs in clinical practice by providing sex-specific threshold values. In this scenario, the current review aims to gather the available knowledge on sex-related differences in MMPs levels in CVDs and CNS conditions, hoping to shed light on their use as sex-specific biomarkers of disease prognosis or progression.

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Section: Sex Differences In Mmps and Pathologiesmentioning

confidence: 85%

Section: Sex Differences In Mmps and Pathologiesmentioning

confidence: 99%

Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases

Trentini

Manfrinato

Castellazzi

et al. 2022

JPM

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Greater TIMP‐1 protein levels and neointimal formation represent sex‐dependent cellular events limiting aortic vessel expansion in female rats

Al‐Katat,

Boudreau,

Gagnon

et al. 2024

IUBMB Life

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Fragmentation/loss of the structural protein elastin represents the precipitating event translating to aortic expansion and subsequent aneurysm formation. The present study tested the hypothesis that greater protein expression of tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1) and neointimal growth secondary to a reduction of medial elastin content represent sex‐dependent events limiting aortic vessel expansion in females. TIMP‐1 protein levels were higher in the ascending aorta of female versus male patients diagnosed with a bicuspid aortic valve (BAV). The latter paradigm was recapitulated in the aorta of adult male and female rats complemented by greater TIMP‐2 expression in females. CaCl2 (0.5 M) treatment of the infrarenal aorta of adult male and female rats increased the in situ vessel diameter and expansion was significantly smaller in females despite a comparable reduction of medial elastin content. The preferential appearance of a neointimal region of the CaCl2‐treated infrarenal aorta of female rats may explain in part the smaller in situ expansion and neointimal growth correlated positively with the % change of the in situ diameter. Neointimal formation was secondary to a significant increase in the density of medial/neointimal vascular smooth muscle cells (VSMCs) that re‐entered the G2‐M phase whereas VSMC cell cycle re‐entry was attenuated in the CaCl2‐treated infrarenal aorta of male rats. Thus, greater TIMP‐1 expression in the aorta of female BAV patients may prevent excessive elastin fragmentation and preferential neointimal growth following CaCl2‐treatment of the infrarenal aorta of female rats represents a sex‐dependent biological event limiting vessel expansion secondary to a significant loss of the structural protein.

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