Alterations in Gene Expression of Components of the Renin-Angiotensin System and Its Related Enzymes in Lung Cancer

Figures

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  Figure 1. Pathways of the renin-angiotensin system (RAS) cascade. The classical RAS cascade is shown with light shading and includes the two major angiotensin II receptor subtypes, AT1 and AT2. Nonclassical components of the RAS cascade would include the ability of the (pro)renin receptor to activate prorenin, as well as enhance the activity of renin to metabolize angiotensinogen to Ang I, the ability of chymase to convert Ang I to Ang II, metabolism of Ang II to III and III to IV by aminopeptidases A and N, respectively, and the novel AT4 receptor for Ang IV which is also known as insulin-regulated aminopeptidase. In addition, there is the ACE2/Ang 1–7/mas axis of the RAS which is considered to be a counterregulator of the actions of the classical RAS. This includes the enzyme angiotensin-converting enzyme 2 (ACE2) which primarily forms Ang 1–7 from Ang II, but can also form Ang 1–9 from Ang I, prolylcarboxypeptidase which also forms Ang 1–7 from Ang II, and the enzymes neprilysin and prolylendopeptidase which forms Ang 1–7 directly from Ang I, and MAS, the putative receptor for Ang 1–7. The names of the genes that encode the various proteins of the RAS and related proteins are shown in…

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  Figure 2. Expression of genes of proteins that comprise the classical renin-angiotensin system. Gene expression in normal lung tissue (open bars n = 49) and lung tumor tissue (solid bars, n = 58) is expressed as Log2 values. AGT encodes angiotensinogen, REN encodes renin, ACE encodes angiotensin-converting enzyme, AGTR1 encodes the AT1 Ang II receptor subtype, and AGTR2 encodes the AT2 Ang II receptor subtype. ∗p < 0.05 by unpaired t test with Welch's correction for heterogeneity of variance and Sidak's correction for multiple comparisons, ∗∗p < 0.01 by unpaired t test with Welch's correction for heterogeneity of variance and Sidak's correction for multiple comparisons.

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  Figure 3. Expression of genes of proteins that directly interact with renin-angiotensin system. These genes encode proteins that can alter the function of RAS but have many other functions. ATP6AP2 encodes the prorenin receptor (ATPase H(+)-transporting accessory protein 2), CMA1 encodes chymase, LNPEP encodes the Ang IV (AT4) receptor (insulin-regulated aminopeptidase), ENPEP encodes aminopeptidase A, and ANPEP encodes aminopeptidase N. One value for ANPEP was excluded from the data analysis because it was >3 standard deviations apart from the rest of the dataset. ∗p < 0.05 by unpaired t test with Welch's correction for heterogeneity of variance and Sidak's correction for multiple comparisons.

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  Figure 4. Expression of genes of ACE2/Ang 1–7/MAS axis of the renin-angiotensin system. Expression of genes encoding proteins of the ACE2/Ang 1–7/MAS axis of the RAS which is an arm of the RAS that generally counteracts the actions of the classical RAS. ACE2 encodes angiotensin-converting enzyme-2, MME encodes neprilysin (neutral endopeptidase), PRCP encodes prolylcarboxypeptidase, PREP encodes prolylendopeptidase, and MAS1 encodes MAS (Ang 1–7 receptor). ∗∗p < 0.01 by unpaired t test with Welch's correction for heterogeneity of variance and Sidak's correction for multiple comparisons.