What is the clinical evidence from this study?

Study design: Other. Population: Heart failure. Intervention: T8Ab (anti-ANTXR1 antibody) vs. Vehicle. Primary outcome: Survival post-myocardial infarction.

October 2, 2025Nature Cardiovascular Research1 citationsOpen Access

ANTXR1 blockade enhances cardiac function in preclinical models of heart failure

NBNicola BoccellaNational Cancer Institute GYGuojun YuFrederick National Laboratory for Cancer Research SSSteven SeamanFrederick National Laboratory for Cancer Research

Key Result

ANTXR1 pharmacological blockade with T8Ab improved survival to 67% compared to 35% with vehicle and enhanced cardiac function in preclinical models of heart failure.

Structured PICO

Does ANTXR1 blockade improve cardiac function and survival in preclinical models of heart failure?

Population

Preclinical mouse models of heart failure (C57BL6 mice), including acute myocardial infarction (MI), angiotensin II/phenylephrine (ATII/PE)-induced hypertension, and high-fat diet/L-NAME (HFD/L-NAME)-induced obesity HFpEF, as well as fibroblast-specific Antxr1 knockout mice.

Intervention

ANTXR1 pharmacological blockade using human neutralizing antibody T8Ab (15 mg/kg intraperitoneally 3 times per week) or genetic disruption of Antxr1.

Comparator

Vehicle treatment or wild-type (Fib-WT) controls.

Outcome

Cardiac function (ejection fraction, global longitudinal strain, MV E/e' ratio) and survival.surrogate

ANTXR1 blockade prevents and reverses cardiac dysfunction in preclinical models of ischemic, hypertensive, and obesity-induced heart failure by modulating cardiac fibroblast activation and collagen turnover.

Main Result

Absolute Event Rate: 67% vs 35%

Abstract

Heart disease, a leading cause of mortality worldwide, is in urgent need of improved therapies. Fibrosis, an accumulation of collagen-rich extracellular matrix in response to injury, is a hallmark of heart disease, but clinical agents that can interfere with the fibrotic pathway do not yet exist. Here we show that ANTXR1/TEM8, a pathology-induced transmembrane protein required for collagen removal, exacerbates injury in multiple models of heart failure. Genetic disruption of Antxr1 and treatment with human neutralizing antibodies prevented heart deterioration following acute myocardial infarction. ANTXR1 pharmacological blockade also improved heart function in models of pressure overload and obesity-induced heart disease with preserved ejection fraction. Improved heart function was accompanied by enhanced exercise tolerance. Mechanistic studies revealed an ANTXR1-antibody-driven improvement in post-infarct scar formation followed by attenuation of late-stage, chronic TGFβ-mediated extracellular matrix remodeling. Thus, ANTXR1-mediated collagen turnover during heart failure is both maladaptive and druggable, providing avenues for therapeutic intervention.

Ask AI

Helpful

Bookmark

View Full Paper