Maria J Sanchez Quintero

Instituto de Investigacion Biomedica de Malaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAN

Abstract Title: Modeling Pulmonary Arterial Hypertension Metabolism Using Patient-Derived Skin Fibroblasts

Biography:

I earned my PhD at IBIMA (University of Málaga) in 2013, studying inflammatory mechanisms in drug allergy. Afterward, I pursued postdoctoral training in the U.S., first at the University of Hawaiʻi, focusing on malaria immunopathogenesis, and later at Columbia University, investigating mitochondrial diseases and bioenergetics. Since 2020, as a postdoctoral researcher at CIBERCV and IBIMA-Plataforma Bionand, I have led independent projects on mitochondrial metabolism in cardiovascular diseases. My current work focuses on pulmonary hypertension, developing the first in vitro model to study mitochondrial dysfunction. Internationally, I participate in four COST Actions, promoting European collaboration and knowledge exchange.

Research Interest:

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by vascular remodeling, in which metabolic dysregulation and oxidative stress are key contributors. Studying these mechanisms in humans has been limited by dependence on surgical specimens or animal models. Here, we describe a novel non-invasive in vitro model based on dermal fibroblasts from PAH patients, enabling the assessment of disease-associated molecular alterations. Fibroblasts were obtained from PAH patients (n = 10) and healthy controls (n = 10) through skin biopsy and cultured under basal conditions or in glucose-free medium for 48 hours. Gene expression of GDF15 (cellular/mitochondrial stress), PGC1α (mitochondrial biogenesis), NRF2 (antioxidant response), and LDHA (glycolysis) was analyzed by RT-qPCR. Patient-derived fibroblasts exhibited increased GDF15, NRF2, and LDHA expression and reduced PGC1α compared with controls, indicating enhanced stress responses and a glycolytic shift consistent with previous findings in pulmonary vascular cells. Under glucose deprivation, NRF2 and LDHA expression remained stable in patient cells but rose in controls, reaching comparable levels—suggesting chronic activation of these pathways in patients versus inducible activation in controls. Elevated LDHA expression supports a Warburg-like metabolic phenotype, potentially reversible upon glucose withdrawal. This represents the first in vitro model derived from PAH patient fibroblasts, recapitulating hallmark molecular alterations such as mitochondrial dysfunction, oxidative stress, and enhanced glycolysis. The model offers a non-invasive, reproducible, and clinically relevant platform to investigate disease mechanisms and to evaluate novel therapeutic approaches for PAH.