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endothelial cells and cardiovascular disease

Endothelial Cells and Cardiovascular Disease

Endothelial cells line the blood and lymphatic vessels of the body. They do much more than simply function as a lining, however. Endothelial cells are critical for maintenance of vessel function, tone, blood pressure, and angiogenesis. Endothelial cells actively receive signals from the blood and relay them to the vessel, and signal back to the blood in response. These signals can affect blood flow, causing vessels to dilate or contract depending on the context. Factors, such as smoking and diabetes, cause an inflammatory environment within the blood vessels. This adversely affects endothelial cells, disrupting their proper function, which can lead to cardiovascular disease.

Recent Research Featuring Lifeline® Endothelial Cells

Zhong et al. were interested in the role of microRNAs (miRNAs) in metabolic memory, a phenomenon that occurs in diabetes where glycemic control is “remembered” by the vasculature, so that the harmful effects of hyperglycemia are attenuated. The researchers used Lifeline® human aortic endothelial cells (HAECs) to induce an in vitro model of hyperglycemia and metabolic memory by exposing cells to high glucose for the extent of the experiment (hyperglycemia), or by exposing cells to high glucose for one day and normal glucose for the remaining six days. They identified three miRNAs that were significantly different between the two groups: miR-125b was upregulated during metabolic memory, while miR-29a-3p and miR-146a-5p were downregulated during metabolic memory. Additionally, these three miRNAs are also implicated in the NF-kB pathway, which is upregulated in response to hyperglycemia in HAECs. They found that miR-125b decreases TNFAIP3 protein levels, resulting in activation of NF-kB signaling. The researchers also identified two targets of miR-146a-5p: IRAK1 and TRAF6, which also serve to activate NF-kB signaling when expressed. Therefore, this study demonstrates that miRNAs are important in the activation of NF-kB signaling in the process of metabolic memory.

Zhang et al. investigated the beneficial effects of Lycium barbarum on salt-sensitive hypertension. L. barbarum is a boxthorn plant that has been used in Chinese medicine to treat a number of ailments. The active element of L. barbarum is thought to be Lycium barbarum polysaccharide (LBP), which has antioxidant and protective effects in experimental models. Here, the researchers evaluated the beneficial effects of LBP on a rat model of salt-sensitive hypertension and in Lifeline® human umbilical vein endothelial cells (HUVECs) grown in high salt conditions. They found that L. barbarum treatment decreased systolic blood pressure of rats on a high salt diet, and this was associated with increased endothelial nitric oxide synthase (eNOS) expression. Similar to the rat model, Lifeline® HUVECs treated with LBP following high salt conditions exhibited increased eNOS expression, compared to HUVECs treated with high salt conditions alone. The authors also observed increased lncRNA sONE expression in high salt conditions in their models. LncRNA sONE can disrupt eNOS mRNA expression, but its levels were decreased upon L. barbarum and LBP treatment, suggesting that LBP may increase eNOS expression through this mechanism. Together, these results suggest that L. barbarum and its active component, LBP, could have beneficial effects on salt-sensitive hypertension by affecting eNOS expression, which in turn, regulates nitric oxide production, a critical regulator of blood pressure.

Cigarette smoke can lead to cardiovascular disease, leading to an increased effort to define the mechanism by which toxins in cigarette smoke affect the cardiovascular endothelium. However, there has been debate about the relevancy of current in vitro models used to test the effects of cigarette smoke. In particular, these models may not replicate the concentration of toxins within smoke and importantly, may not have the essential metabolites present. McQuillan et al. set out to develop a better in vitro model system to test the effects of cigarette smoke on the cardiovascular endothelium. They hypothesized that human sera may be an applicable medium to test smoke toxins as it more closely mimics the endogenous environment. The researchers exposed Lifeline® HUVECs grown in VascuLife® medium to sera from either smokers or non-smokers and evaluated the effects. They found that in a scratch assay, cells exposed to smokers’ sera migrated more slowly than cells exposed to non-smokers’ sera. Additionally, HUVECs exposed to smokers’ sera expressed increased cardiovascular disease- and inflammation-associated genes and proteins. The researchers conclude that exposure to human sera from smokers is a good model for defining the mechanism by which smoking contributes to cardiovascular disease.

Diabetes can affect normal endothelial cell function and contribute to cardiovascular disease. In particular, diabetes results in the presence of advanced glycation end products (AGEs), the receptor for which (RAGE) is expressed on the surface of endothelial cells. RAGE activation causes F-actin reorganiziaton, which prevents resealing of the plasma membrane, although the mechanism is unclear. In a recent study, Kim and Kwon investigated the role of thymosin beta 4 (Tb4), a small peptide, in protecting cells against the effects of RAGE in Lifeline® HUVECs. They observed that Tb4 treatment decreased the toxicity induced by AGE treatment, as well as decreased the expression of RAGE itself. The authors hypothesized the mechanism behind this is due to Tb4’s ability to decrease the F-actin to G-actin ratio, which in turn, affects RAGE expression. Additionally, Tb4 increased the ability of HUVECs to form vessel-like tube structures following AGE treatment when grown on Matrigel. Together, the results of this study suggest that Tb4 counteracts the deleterious effects of RAGE activation through cytoskeletal rearrangements, and that Tb4 may be a potential therapeutic opportunity for AGE-induced diabetic complications.

Normal Human Endothelial Cell Types from Lifeline®

Lifeline® offers many endothelial cell types from multiple origins, all optimized for growth in VascuLife® endothelial medium. They include:

We are always interested in hearing from our customers! Tell us how you are using Lifeline® cells to answer your research questions and your study could be featured here on our blog!

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