Author + information
- Dimitri Arangalage, MD, PhD,
- Antonino Nicoletti, PhD,
- Giuseppina Caligiuri, MD, PhD and
- Jamila Laschet, PhD∗ ()
- ↵∗INSERM U 1148, Bichat Hospital, 46 rue Henri Huchard, 75018 Paris, France
We thank Dr. Ma and colleagues for their interest in our recent publication (1) and for their contribution to this exciting discussion.
First, we would like to remove an ambiguity. In contrast with the statement of Dr. Ma and colleagues, we reported that endothelial microfissuring not only occurs in calcified valves, but also in noncalcified ones (1). Therefore, the microfissuring due to mechanical stress, to which all valves are subjected, is likely not sufficient, per se, to trigger the cascade of pathological events that ultimately leads to valve calcification. We postulate that, rather than the occurrence of acute wounding, the failure to cope with repeated injury of the valve endothelium and of the associated entry of blood within the aortic valve leaflets is the culprit trigger of the pathological local tissue remodeling leading to irreversible fibrosis through to the calcification stage. Indeed, the quality of tissue-infiltrated blood itself may determine the issue of the healing following the occurrence of each microfissure. Hence, the presence of soluble blood elements able to interfere with the sequence of events required for effective tissue healing may compromise, at certain occasions, the physiological repair processes of aortic valve endothelial wounds. Interventions capable of limiting the extent of intraleaflet hematomas and/or of promoting their effective resorption by driving, for example, effective intravalve efferocytosis and/or resolution of the inflammatory phase of the repair processes, certainly represent promising strategies to limit the local inflammatory response and the ensuing pathological sequence leading to aortic valve calcification.
In agreement with the suggestion of Dr. Ma and colleagues, we believe that genetic risk factors and/or soluble blood components, such as lipoprotein(a) or inflammatory cytokines, may affect this wound healing process and promote calcification (2). It is, therefore, of utmost importance to move toward multiomic translational studies relying on large cohorts of patients to identify environmental and genetic predisposing factors linking inappropriate local responses to microfissuring events to the development of calcific aortic stenosis.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation
- Morvan M.,
- Arangalage D.,
- Franck G.,
- et al.
- Yu B.,
- Hafiane A.,
- Thanassoulis G.,
- et al.