Abstract
Cardiovascular diseases, followed by strokes, represent the leading cause of mortality worldwide. Despite its success in preventing cardiovascular diseases, the therapeutic potential of 3-Hydroxytyrosol (HT) for treating ischemic diseases is yet to be investigated in detail, especially with regard to ischemic heart disease, which is a major challenge for humans. We assessed that low concentrations (1–5 µM) of HT, generally achieved after the ingestion of olive oil, stimulate endothelial cells migration and angiogenesis in an in vitro model. At early time points (1–6 h), HT induces the expression of different proteins such as proto-oncogene tyrosine-protein kinase Src (Src), rho-associated protein kinase (ROCK) and matrix metalloproteinase-2 (MMP-2) protein influencing cell adhesion, cytoskeletal dynamics and cell migration. We observed that at the same time, HT induces prominent vascular formation in the tube formation assay, accompanied by an increase in the expression of the vascular endothelial growth factor receptor (VEGF-R2) and PI3K-Akt-eNOS protein pathways, which are recognized for their central role in angiogenesis. Therefore, in addition to the proven capability of HT to regulate reactive oxygen species (ROS) levels, through both direct scavenging properties and indirect antioxidant efficacy, our results revealed that HT promotes angiogenesis, arguing in favor of great pharma-nutritional potential in ischemic injuries.
Highlights
Cardiovascular diseases are a group of different disorders affecting heart and blood vessels—primarily arteries supplying blood to the heart, brain and other organs—that lead to acute complications responsible for ischemic conditions
In order to study the effects of 3-Hydroxytyrosol (HT) on angiogenesis, we used a well-characterized cell line of human umbilical vascular endothelial cells (HUVEC)
One of the major limitations found in the clinic compared to preclinical models is represented by the different recovery capacity in the vascularization of animal models compared to patients, where the increase in the capillary bed may not be enough to guarantee the recovery of hard-hit or necrotic ischemic tissues
Summary
Cardiovascular diseases are a group of different disorders affecting heart and blood vessels—primarily arteries supplying blood to the heart, brain and other organs—that lead to acute complications responsible for ischemic conditions. It is well recognized that the Mediterranean diet, which is characterized by an abundant intake of vegetables, fruit, legumes, cereals, fish, etc., is associated with increased longevity and improved cognitive function, and has proven cardio-protective action [2]. It is associated with a reported lower incidence of chronic degenerative diseases, as well as anti-tumor and anti-inflammatory properties [3]. The Mediterranean alimentary pattern displays beneficial effects in healthy people, and represents a good basis for the prevention of numerous diseases and protection against overall morbidity and mortality
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