Pyogenic granuloma, an impaired wound healing process, linked to vascular growth driven by FLT4 and the nitric oxide pathway

Abstract

Pyogenic granuloma, also called lobular capillary hemangioma, is a condition usually occurring in skin or mucosa and often related to prior local trauma or pregnancy. However, the etiopathogenesis of pyogenic granuloma is poorly understood and whether pyogenic granuloma being a reactive process or a tumor is unknown. In an attempt to clarify this issue, we performed genome-wide transcriptional profiling of lasercaptured vessels from pyogenic granuloma and from a richly vascularized tissue, placenta, as well as, from proliferative and involutive hemangiomas. Our study identified a gene signature specific to pyogenic granuloma. In the serial analysis of gene expression (SAGE) database, this signature was linked to 'white blood cells monocytes'. It also demonstrated high enrichment for gene ontology terms corresponding to 'vasculature development' and 'regulation of blood pressure'. This signature included genes of the nitric oxide pathway alongside genes related to hypoxia-induced angiogenesis and vascular injury, three conditions biologically interconnected. Finally, one of the genes specifically associated with pyogenic granuloma was FLT4, a tyrosinekinase receptor related to pathological angiogenesis. All together, these data advocate for pyogenic granuloma to be a reactive lesion resulting from tissue injury, followed by an impaired wound healing response, during which vascular growth is driven by FLT4 and the nitric oxide pathway.

Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies

“…Reactive vascular proliferative lesions were grouped with benign tumors. The distinction between the reactive or tumor nature of a lesion is not always straightforward and is debated for several lesions (pyogenic granuloma/ lobular capillary hemangioma, 16 spindle cell hemangioma, 17 epithelioid hemangioma 18 ). Some rare vascular tumors are not included in the table and are listed as "others,"…”

Giant Pyogenic Granuloma in a Patient with Chronic Lymphocytic Leukemia

“…Interestingly, drug-associated pyogenic granulomas tend to have a periungual and subungual distribution [10]. Recent insights from gene expression profiling identify FLT4 (a specific VEGF receptor), the nitric oxide pathway and vascular injury and repair pathways as specifically upregulated in pyogenic granulomas compared to other vascular proliferative lesions [12]. How the molecular underpinnings connect to the diverse set of reported triggers remains unclear.…”

Successful Treatment of Suborbital Pyogenic Granuloma with Topical Imiquimod

“…A recent genetic study on vessels derived from cutaneous PG lesion identified a gene signature including genes of the nitric oxide pathway and those related to hypoxia-induced angiogenesis and vascular injury, like the tyrosine-kinase receptor FTL4 [18]. Thus, PG may be regarded as a reactive lesion resulting from tissue injury, followed by an impaired wound healing response, during which vascular growth is driven by FLT4 and the nitric oxide pathway.…”