Cellular models to study the cardiac System (part I)

In this post, I’d like to  introduce human aortic, brachiocephalic, carotid artery and coronary artery cells isolated by Cell Applications Inc. In a future post, I’ll be highlighting human internal thoracic artery, pulmonary artery, subclavian artery cells and cardiomyocytes (now published here).

After taking a look at several cell types as models for studying different aspects of cardiovascular functions and diseases, I’ll cover some recently published results highlighting the importance of securing your primary cells sourcing.

Human Aortic Cells

Human Aortic Endothelial Cells

Human Aortic Endothelial Cells (HAOEC) provide an excellent model system to study all aspects of cardiovascular function and disease, and they have been utilized in dozens of research publications to study diabetes-associated complications related to cardiovascular function, investigate mechanisms of immune response and graft rejection, study endothelial dysfunction caused by air pollution, oxidative stress and inflammation, and develop 3d endothelialized engineered tissues, as well as new technologies based on novel material surfaces and drugs in order to reduce risks associated with vascular implants.

Human Aortic Smooth Muscle Cells

Human Aortic Smooth Muscle Cells (HAOSMC) provide an excellent model system to study all aspects of cardiovascular function and disease, especially those related to mechanisms of hyperplasia and hypertrophy of intimal smooth muscle cells leading to vascular occlusion in atherosclerosis and stent restenosis.

HAOSMC from Cell Applications, Inc. have been utilized in dozens of research studies, for example, to: elucidate cytokines and growth factors signaling pathways implicated in the molecular regulation of smooth muscle cell proliferation, migration, and overall vascular function (Liu, 2009; Tan, 2009; Seymour, 2010; Chen, 2011; Hirase, 2013; Stein, 2013).

Human Brachiocephalic Artery Cells

Human Brachiocephalic Artery Endothelial Cells (HBcAEC)  (along with human aortic (HAOEC), carotid artery (HCtAEC), coronary artery (HCAEC) and subclavian artery (HScAEC), all from Cell Applications, Inc., have been used to demonstrate that not only blood vessels from different tissues are highly heterogeneous, they also interact differently with leukocytes during the inflammation response (Scott, 2013).  The authors further showed that differential N-glycosylation of commonly expressed vascular adhesion molecules may be responsible for this heterogeneity, as well as for modulation of signaling under resting and activated inflammatory conditions.  This also explains why specific vascular beds may be more or less susceptible to particular diseases or stimuli.

Human Brachiocephalic Artery Smooth Muscle Cells

Human Brachiocephalic Artery Smooth Muscle Cells (HBcASMC) provide a useful in vitro system to study all aspects of cardiovascular function and disease, especially those related to mechanisms of hyperplasia and hypertrophy of intimal smooth muscle cells leading to vascular occlusion in atherosclerosis and stent restenosis.

Human Carotid Artery Cells

Human Carotid Artery Endothelial Cells (HCtAEC) obtained from Cell Applications, Inc. have been used to elucidate molecular mechanisms of cerebral aneurism caused by haemodynamic (sheer) stress and inflammation, which were shown to act through PGE2-EP2 and NF-κB signaling (Aoki, 2011). Demonstrating a link between inflammation and neovascularization, serum amyloid A, a biomarker of inflammation, increased expression of TNF, F3 factor, NF-κB and VEGF leading to activated migration, wound healing and tube formation responses in HCtAEC; these pro-angiogenic activities could be prevented by pretreatment with the multi-angiokinase receptor inhibitor BIBF1120 (Cai, 2013). Additionally, CD40-CD154 signaling between endothelial cells and T cells leads to a stress response in endothelial cells via activation of NF-κB and MAPK/SAPK pathways and induces down-regulation of APLN, while at the same time activating viral immune surveillance system involving TLR3, IFIH1, RIG-I, and RNASEL (Pluvinet, 2008).

Human Carotid Artery Smooth Muscle Cells

Human Carotid Artery Smooth Muscle Cells (HCtASMC) provide a useful in vitro system to study all aspects of cardiovascular function and disease, especially those related to mechanisms of hyperplasia and hypertrophy of intimal smooth muscle cells leading to vascular occlusion in atherosclerosis and stent restenosis.

Human Coronary Artery

Human Coronary Artery Endothelial Cells (HCAEC) from Cell Applications, Inc. provide an excellent model system to study all aspects of cardiovascular function and disease, and they have been utilized in dozens of research publications, for example to:

• Understand the mechanism of the anti-inflammatory properties of HDL, and demonstrate for the first time that mature miRNA can control gene expression in a cell where it is neither transcribed nor processed (Tabet, 2014);
• Study mechanisms of angiogenesis, as well as oxidative stress and inflammation related pathways in endothelia (Ji, 2009; Wang, 2011; Quinn, 2011; Hung, 2010; Rajesh, 2010; Riegel, 2011; Lin, 2013; Lloid, 2013Baley-Downs, 2012; Kapur, 2012; Melchior, 2012; Castanares-Zapatero, 2013; Hankins, 2013; Lord, 2013; dela Paz, 2013; Takai, 2013), including gender and race specific differences in patients with peripheral artery disease (Gardner, 2014);
  elucidate molecular mechanisms of various cardiovascular risk factors, including those associated with diabetes (Vladik, 2011; Kapur, 2011; Dunn, 2013; Leucker, 2013; Liu, 2013, 2014; Morgan, 2014; Torella, 2014);
• Understand the mode of action and cardiovascular protection effects of various natural compounds, vitamins and drug candidates (Candelario, 2013; Ramirez-Sanchez, 2010, 2013; Lee, 2013; Nsimba, 2013; Di Bartolo, 2011; Baotic, 2013; Murphy, 2013; Tan, 2013; Wu, 2012), as well as caloric restriction (Csiszar, 2009, 2013);
  develop and evaluate scaffolds and hydrogels for cardiac tissue engineering (Singelyn, 2009, 2011; Seif-Naraghi, 2010; Johnson, 2014), and new treatment strategies to prevent stent restenosis (O’Neill, 2009; O’Brien, 2010; Crowder, 2011, 2012; Eppihimer, 2013; Hiob, 2013);
• Compare effects of BMP-4 on HCAEC and Human Pulmonary Artery Endothelial Cells (HPAEC) and show that only in HCAEC BMP-4 treatment induced ROS, activated NF-kB, ICAM-1 and increased monocyte adhesiveness, explaining why its upregulation leads to atherosclerosis and hypertension in the systemic, but not pulmonary circulation (Csiszar, 2008).

Human Coronary Artery Smooth Muscle Cells

Human Coronary Artery Smooth Muscle Cells (HCASMC) provide an excellent model system to study all aspects of cardiovascular function and disease, especially those related to mechanisms of hyperplasia and hypertrophy of intimal smooth muscle cells leading to vascular occlusion in atherosclerosis and stent restenosis.

HCASMC from Cell Applications, Inc. have been utilized in a number of research studies, for example, to:

• Study signaling pathways regulating smooth muscle differentiation (Zhou, 2010); and chronic inflammation of arterial wall that leads to artherosclerosis (Kiyan, 2014);
• Demonstrate that STAT-1 and STAT-3 regulate VEGF production in smooth muscle cells by having opposing effects on HIF-1α expression (Albasanz-Puig, 2012); study the mechanisms of hypoxia and reoxigenation injuries in by demonstrating increased production of ROS and inflammatory cytokines, and further showing that DHA is not beneficial in this type of injuries (Feng, 2012);
• Investigate (by also using human Internal Thoracic Artery Smooth Muscle Cells obtained from Cell Applications, Inc.), the gene expression differences between smooth muscle cells from different arteries, underlying their differential response to injuries and proliferation stimuli (Lange, 2013);
• Suggest the hypermethylation of SOCS3 gene as the connection between TNF-α and IGF-1 released in response to mechanical injury during coronary intervention, and the induction of cytokines leading to intimal hyperplasia and restenosis (Dhar, 2013);
• Develop a novel VEGFR/MET-targeted inhibitor with improved antitumor efficacy and decreased toxicity (Fujita, 2013); and investigate novel therapies and drug combinations to achieve optimal target selectivity (Lehar, 2009; Wo-Wong, 2013);
• Develop elastic scaffolds for tissue engineering (Nivison-Smith, 2010, 2012) and novel treatment strategies to prevent stent restenosis by designing new materials (Crowder, 2012), or drug therapies to preferentially inhibit smooth muscle cell growth (O’Neill, 2009; Mociornita, 2013).

Primary cells for research

Because of the complex heterogeneity that exists not only between different donors, but even between different vascular beds in the same individual, it would be prudent to confirm any new findings on primary cell lots coming from several different origins.

To illustrate this, Scott et al. (Scott, D.W., M.O. Vallejo, and R.P. Patel. 2013. Heterogenic endothelial responses to inflammation: role for differential N-glycosylation and vascular bed of origin. Journal of the American Heart Association. 2:e000263-e000263) demonstrated that not only blood vessels from different tissues are highly heterogeneous, they also interact differently with leukocytes during the inflammation response using HCAEC, HAOEC, HCtAEC, HScAEC and HBcAEC (Cell Applications Inc.). The authors further showed that differential N-glycosylation of commonly expressed vascular adhesion molecules may be responsible for this heterogeneity, as well as for modulation of signaling under resting and activated inflammatory conditions. This also explains why specific vascular beds may be more or less susceptible to particular diseases or stimuli. Importantly, if cells from different sources were used, these results could not be convincingly validated due to a number of uncontrolled variables, such as age, race, genetic variability or life style choices of the donors. To eliminate the donor-to-donor variability, the scientists took advantage of the great variety of primary cells offered by Cell Applications, including the option of ordering a panel of endothelial cells obtained from different vascular beds of the same donor!

It’s important to find a reliable source, and preferably one offering a large selection of cell types and associated media, for whatever technical application and thematics you’re working on: flow based assays, primary and secondary screening, stem cell studies, diabetis & obesity, cosmetology, electrophysiology, cell imaging, bio-banking…

Points to bear in mind… you want to be sure of getting:

• Access to large and regularly updated lot inventories
• Same cell types from various species
• Arrays of cell types from the same donors
• Lot reservation pending testing & validation

Which cell types are you looking for? The tebu-bio group (their headquarters are in France, but one of their local specialists across Europe is bound to be near you!), offer among their broad range of products: Islet cells, sebocytes, neurones, endothelial & epithelial cells, cardiomyocytes, fibroblasts, keratinocytes, melanocytes…

Get in touch with their Cell Specialists to learn more!