## 5 LncRNAs in Cardiovascular Development  
It is becoming more evident that lncRNAs play important roles in cardiovascular development and embryogenesis [34,35]. In fact, lncRNAs regulate the processes that sustain cell transformation and organogenesis. During organogenesis, lncRNAs regulate genes and miR that are activated during cell fate and cell maintenance to ensure a proper development and cellular transformation [35]. LncRNAs are essential components of the regulation of genes in embryonic stem cells because alteration of gene expression may cause an imbalance in the maintenance of stem cell differentiation [36]. For example, the cellular pluripotency is correlated with the expression of lncRNAs that are regulated by transcription factors such as Nanog and octamer-binding transcription factor 4 (Oct4) [37].  
LncRNAs also play crucial roles in mammalian heart development and cellular lineage. In a study conducted in mice, Bvht was found to participate in cardiovascular-associated cell differentiation. The study revealed that Bvht was required for the development of nascent mesoderm, which influenced cardiac growth and activated a network of genes associated with cardiac differentiation. Also, Bvht was involved in cardiomyocyte differentiation and was shown to modulate cell fate in neonatal cardiomyocytes (Table 1 and Figure 3) [9].  
\begin{table}
\begin{tabular}{c c c c} \hline
**Disease** & **LncRNA Name** & **Effect *** & **Reference** \\ \hline \multirow{4}{*}{Atherosclerosis} & CDKNA/B & \(\uparrow\) & [38] \\  & DYN-LRB2-2 & \(\uparrow\) & [39] \\  & RP5-833A20.1 & \(\uparrow\) & [40] \\ \hline \multirow{2}{*}{Cardiac Hypertrophy} & CHRF & \(\uparrow\) & [10] \\  & MHRT & \(\uparrow\) & [41] \\ \hline Heart Failure & LIPCAR & \(\downarrow\)/\(\uparrow\) & [42] \\ \hline Coronary Artery Disease & ANRIL & Unknown & [43] \\ \hline Ischemia andreperfusion & UAC1 & \(\downarrow\) & [44] \\ \hline \multirow{4}{*}{Cardiac Development} & BVHT & \(\uparrow\) & [9] \\  & TERMINATOR & \(\downarrow\) & [45] \\  & ALIEN & Unknown & [45] \\  & AK143260 & Unknown & [45] \\  & FENDRR & Unknown & [46] \\ \hline \multirow{4}{*}{Myocardial Infarction} & MIAT & Unknown & [47] \\  & APF & \(\uparrow\) & [48] \\ \cline{1-1}  & ANRIL & Unknown & [43] \\ \cline{1-1}  & MIRT1 & \(\uparrow\) & [49] \\ \cline{1-1}  & MIRT2 & \(\uparrow\) & [49] \\ \hline \end{tabular}  
* \(\uparrow\): up-regulation; \(\downarrow\): down-regulation.  
\end{table}
Table 1: LncRNAs associated with cardiovascular development and diseases.  
It has been also shown that lncRNAs interact with coded genes to regulate cellular lineage. During stem cell differentiation, cells lacking lncRNA AK143260 do not differentiate into specific cardiac cells. AK143260 is important for the activation of a gene network which is involved in the transition of cardiac mesoderm into multipotent cardiac cell progenitors [45]. Moreover, lncRNA TERMINATOR controls the identity of pluripotent stem cells and alters the function of lncRNA ALIEN, which is related to cardiovascular development (Table 1 and Figure 3) [45]. The expression of lncRNA PUNISHER compromises the functions of cardiac endothelial cells and lncRNA Bvht controls _MesP1_ gene, which is a master regulator of genes that modulate the differentiation of cardiac cells in vertebrates [45,50]. It has been also demonstrated that lncRNA Bvht interacts with the polycomb repressive complex 2 (PRC2), which has histone methyl-transferase activity [51]. The PRC2 modulates _MesP1_ and other important genes for cellular commitment and heart organogenesis [50]. Lastly, lncRNA Fendrr has been shown to be responsible for the development of heart walls [46]. The study from transgenic animal models lacking Fendrr showed that Fendrr controls important transcription factors such as GATA binding protein 6 (GATA-6), NK2 homeobox 5 (NKX2.5), forkhead box f1 (FOXF1), T-box 3 (TBX3), iroquois homeobox 3 (IRX3), and paired-like homeodomain 2 (PITX2) during the heart organogenesis (Table 1 and Figure 3) [46].