Left Ventricular Molecular Signature in Chronic Aortic Regurgitation

Q: What is the clinical evidence from this study?

Population: Chronic aortic regurgitation (n=18). Intervention: Severe chronic aortic regurgitation (induced by retrograde aortic valve perforation) vs. Age-matched control rats (sham/no perforation). Primary outcome: Left ventricular structural, functional, and molecular remodeling at 60 days.

Q: What does this research mean for the field?

Chronic severe aortic regurgitation drives progression to heart failure through coordinated transcriptional alterations in myocardial apoptosis, oxidative stress, metabolic regulation, and calcium-handling pathways. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Bachar El Oumeiri; Laurence Dewachter; P. van de Borne; Géraldine Hubesch; Pascale Jespers; Constantin Stefanidis; Kathleen Mc Entee; Frédéric Vanden Eynden

doi:10.3390/ijms27177950

September 7, 2026International Journal of Molecular SciencesOpen Access

Left Ventricular Molecular Signature in Chronic Aortic Regurgitation

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Key result

Chronic aortic regurgitation drives marked LV dilatation, systolic dysfunction, and widespread adverse transcriptional remodeling.

n=18

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Why the study?

Molecular mechanisms underlying the progression from compensated eccentric hypertrophy to heart failure in chronic aortic regurgitation remain poorly understood.

Does experimentally induced chronic aortic regurgitation cause structural, functional, and transcriptional remodeling in the left ventricle of adult male rats?

Key Points

Investigate myocardial transcriptional changes induced by chronic volume overload during the progression from compensated eccentric hypertrophy to heart failure in severe aortic regurgitation.
Severe aortic regurgitation was induced in male Wistar rats (n = 10) by retrograde aortic valve perforation and compared with age-matched control rats (n = 8).
Cardiac remodeling was assessed 60 days post-surgery using echocardiography, invasive hemodynamics, and left ventricular gene-expression profiling with RT-qPCR.
Chronic aortic regurgitation produced left ventricular chamber dilatation and systolic dysfunction, characterized by significantly reduced fractional shortening and an ejection fraction showing a non-significant trend toward reduction (p = 0.08).
Hearts with aortic regurgitation showed pro-apoptotic and redox transcriptional signaling, demonstrated by an increased BAX/BCL2 ratio, reduced SOD2 expression, and compensatory upregulation of GPX1.
Myocardial metabolic regulation and calcium handling were altered, evidenced by significantly decreased expression of AMPKα1, PPARγ, GLUT4, and SERCA2A, alongside increased expression of OLR1, 15-LOX, and KLK10.

Structured PICO

Does experimentally induced chronic aortic regurgitation cause structural, functional, and transcriptional remodeling in the left ventricle of adult male rats?

P

Population

18 adult male Wistar rats subjected to experimentally induced severe chronic aortic regurgitation or control surgery, followed for 60 days.

I

Intervention

Induction of severe chronic aortic regurgitation by retrograde aortic valve perforation

C

Comparator

Age-matched control rats undergoing control surgery

O

Outcome

Left ventricular structural and functional remodeling (echocardiography, hemodynamics) and myocardial gene-expression profiling at 60 dayssurrogate

This experimental model demonstrates that the transition to decompensated heart failure in chronic aortic regurgitation is accompanied by a multifaceted myocardial transcriptional remodeling response.

Limitations

Conducted exclusively in male rats, precluding assessment of sex-dependent differences
Approximately 30% mortality in the AR group raises the possibility of survivor bias
Molecular analyses were restricted to mRNA expression and do not necessarily reflect protein abundance or biological function
Relatively small sample size may have limited statistical power
Exploratory molecular analyses without formal correction for multiple comparisons
Observational nature of the study precludes establishing causal relationships between molecular alterations and ventricular dysfunction
Conducted exclusively in male rats
30% mortality in the AR group raises possibility of survivor bias
Molecular analyses restricted to mRNA expression
Lack of biochemical and histological analyses for functional confirmation
Small sample size
No formal correction for multiple comparisons
Observational nature precludes establishing causal relationships

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Implication

Rat model data should not change aortic regurgitation practice; leaves open transcriptional targets for future translational studies in volume overload.

Abstract

Molecular mechanisms underlying the progression from compensated eccentric hypertrophy to heart failure in chronic aortic regurgitation (AR) remain poorly understood. We investigated associated transcriptional changes induced by chronic volume overload in an experimental model of severe AR. AR was induced in male Wistar rats (n = 10) by retrograde aortic valve perforation and compared with age-matched control rats (n = 8). Sixty days after surgery, cardiac remodeling was evaluated by echocardiography, invasive hemodynamics and myocardial gene-expression profiling using RT-qPCR. Chronic AR induced marked left ventricular dilatation and systolic dysfunction, consistent with decompensated eccentric hypertrophy. These functional alterations were accompanied by coordinated transcriptional changes involving pathways related to apoptosis, oxidative balance, metabolic regulation and calcium handling. AR hearts exhibited an increased BAX/BCL2 ratio, together with reduced SOD2 and increased GPX1 expression, suggesting a transcriptional profile consistent with activation of pro-apoptotic and antioxidant responses. Metabolic remodeling was characterized by decreased AMPKα1, PPARγ and GLUT4 expression, together with increased OLR1 and 15-LOX. KLK10 expression was increased. Reduced SERCA2A expression was observed, consistent with transcriptional alterations involving calcium-handling pathways. Chronic AR is associated with marked structural and functional cardiac remodeling accompanied by coordinated transcriptional alterations across multiple pathways implicated in myocardial dysfunction. This provides potential molecular pathways for further investigation.

Discussion

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Cite This Study

Oumeiri et al. (2026) studied Chronic aortic regurgitation (n=18). Severe chronic aortic regurgitation (induced by retrograde aortic valve perforation) vs. Age-matched control rats (sham/no perforation) was evaluated on Left ventricular structural, functional, and molecular remodeling at 60 days. Chronic aortic regurgitation induced marked left ventricular dilatation, systolic dysfunction, and coordinated transcriptional alterations across multiple pathways implicated in myocardial dysfunction.

synapsesocial.com/papers/6a9fc6ea684b366da041e528 https://doi.org/10.3390/ijms27177950

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Left Ventricular Molecular Signature in Chronic Aortic Regurgitation

Figures

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Left Ventricular Molecular Signature in Chronic Aortic Regurgitation

Figures

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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