SCD1 has been regarded as the switch between fatty acid storage and consumption as well as in promoting or preventing lipid-induced disorders [9, 10]. SCD1 is involved in the cellular biosynthesis of MUFAs from SFA substrates. The substrates of SCD1 are mainly stearoyl-CoA (C18:0) and palmitoyl-CoA (C16:0), which are desaturated to oleoyl-CoA (C18:1) and palmitoleoyl-CoA (C16:1), respectively. SCD1 prefers to convert stearate to oleate rather than palmitate to palmitoleate , both of which make up the primary storage of unsaturated fatty acids in human adipose tissue . The major MUFAs generated by SCD1 represent the main substrates for synthesis of triglycerides, cholesterol esters and phospholipids. Consistent with its role as a key player in metabolic control, SCD1 activity is tightly regulated, being decreased by unsaturated fatty acids (UFAs) and increased by SFAs .
MSCs were found to differentiate into cartilage, bone, fat, muscle, and other connective tissues [6, 7] depending on the culture conditions, which include supplementation of lineage-specific inducing agents as well as hormones and growth factors. Studies have demonstrated that mesoderm-derived MSCs originate from precursors with angiogenic potential, called mesenchymomagioblasts, which are identified as MS-CFCs with the potential to differentiate into both MSCs and endothelial cells . In endothelial differentiation system, human bone marrow-derived (CD105+, CD29+, CD34–) MSCs are capable of differentiating into endothelial cells in vitro and acquire major characteristics of mature endothelial-like expression of vWF and CD31 . In addition, MSCs give rise to hematopoiesis-supportive stroma and contribute to the formation of the hematopoietic stem cell niche [14, 15] and vascular wall .
In this study, GFP fluorescence imaging showed that BM-MSCs were infected by the packaged virus, and RT-PCR results showed that the expression of SCD1 mRNA of the SCD1 overexpressed group is higher than that of the EV group (p < 0.01). So overexpression of SCD1 in BM-MSCs was achieved successfully. Commonly used markers of the endothelium include CD31 and vWF . Vascular endothelial cadherin (VE-cad), a putative member of the type II subfamily [18, 19] is specifically expressed in endothelial cells and is not found in any other cell type [20, 21]. In order to test the growth of induced endothelial cells, CD31, vWF and VE-cad in MSCs were assayed, and the results of fluorescent quantitative PCR suggested that the mRNA amount of CD31, vWF, VE-cad of the SCD1 overexpressed group was statistically higher than that of the EV group and that of the normal group after 1 week and 2 weeks (p < 0.05). This result indicated that overexpression of SCD1 in BM-MSCs could increases the expression of induced endothelial cells in vitro.
SFAs and lipid oxidation products have been linked with postprandial endothelial dysfunction [4, 22] and atherosclerotic disease. Diets rich in SFAs  or oxidized fatty acids  accelerate the formation of atherosclerotic lesions in animals. High intake of SFAs has been associated with an increased incidence of coronary heart disease (CHD), whereas high intake of MUFAs has been associated with a protective effect [25, 26]. Dietary fats can modify CHD risk by their effect on plasma LDL and HDL cholesterol levels . Consumption of SFAs reduces the anti-inflammatory potential of HDL and impairs arterial endothelial function. Consumption of a Mediterranean-type MUFA-diet produces a decrease in plasma levels of vWF, TFPI and PAI-1 plasma levels in young healthy males. Given that these substances are of endothelial origin, it could be suggested that MUFA of the diet has a beneficial effect on endothelial function .
A large panel of inflammatory genes are regulated by SFAs. A possible role of SFAs in inflammation has been demonstrated in vitro. When stimulating human cells with palmitic acid, the gene expression and protein production of IL-6 increased [29, 30]. The exact mechanisms for these effects are unknown but proposed involved molecules are nuclear factor (NF)-κB and protein kinase C . SFAs represent potential contributors to the vascular inflammation in subjects with metabolic syndrome . In the liver, SCD1 deficiency sensitizes cells to injury . In human myotubes, overexpression of SCD1 enhances triglyceride synthesis and prevents inflammatory and ER-stress responses to palmitate . Overexpression of SCD1 in BM-MSCs might increase the growth of induced endothelial cells by decreasing the amount of SFAs and preventing inflammatory and ER-stress responses.
Study has shown that SCD1 deficiency increases the rate of β-oxidation in soleus and red gastrocnemius muscles by activating of the AMP-activated protein kinase (AMPK) pathway [34, 35]. AMPK leads to phosphorylation and inactivation of acetyl-CoA carboxylase resulting in decreased malonyl-CoA content . Malonyl-CoA is both an intermediate in de novo synthesis of fatty acids and an allosteric inhibitor of carnitine palmitoyltransferase 1 (CPT1), the enzyme that transfers long-chain acyl-CoA molecules from the cytosol to the mitochondria where they are oxidized . A decrease in the cellular levels of malonyl-CoA in the liver and skeletal muscles of SCD1−/− mice would thus derepress CPT1, resulting in increased fatty acid oxidation and downregulation of fatty acid synthesis . High expression of SCD1 is corresponded with low rates of fatty acid oxidation (decreased AMPK activity) . Less fat acid oxidation might reduce inflammatory responses and be beneficial for the growth of induced endothelial cells.
SCD1 deficiency results in increased the phosphorylation of the cAMP response element binding protein (CREBP) and the activation of the peroxisome proliferator activated receptor γ (PPARγ) coactivator-1a (PGC-1a) transcription factor through activation of the β3 adrenergic receptor pathway , resulting in increased activation of uncoupling protein 1 (UCP1) in BAT of SCD1−/− mice. Increased UCP1 expression uncouples oxidative respiration from ATP synthesis, thereby increasing the rate of basal thermogenesis and consequently, whole body energy expenditure, in SCD1−/− mice . Therefore, high expression of SCD1 might decrease the energy expenditure of cells, helping the growth of induced endothelial cells.
It has been demonstrated that SCD1 modulates the passage of cycling cells through the G1/S boundary and the entry into the apoptotic program, and SCD1 regulates mitogenesis by modulating the rate of fatty acid synthesis, by preventing the toxic accumulation of SFA, and by controlling the supply of MUFA substrates required for lipid biosynthesis and cell proliferation . Overexpression of SCD1 in BM-MSCs might contribute to proliferation of induced endothelial cells by modulating the passage of cycling cells .