Editing Coronary artery disease (section)

===[[Transcriptome]]===
Several [[RNA|RNA Transcripts]] associated with CAD - [[FoxP1]], [[ICOSLG]], [[IKZF4/Eos]], [[SMYD3]], [[TRIM28]], and [[TCF3/E2A]] are likely markers of [[regulatory T cells]] (Tregs), consistent with known reductions in Tregs in CAD.<ref>{{cite journal | vauthors = McCaffrey TA, Toma I, Yang Z, Katz R, Reiner J, Mazhari R, Shah P, Tackett M, Jones D, Jepson T, Falk Z, Wargodsky R, Shtakalo D, Antonets D, Ertle J, Kim JH, Lai Y, Arslan Z, Aledort E, Alfaraidy M, Laurent GS | title = RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance | journal = BMC Med Genomics | volume = 14 | issue = 216 | date = September 2021 | page = 216 | pmid = 34479557 | pmc = 8414682 | doi = 10.1186/s12920-021-01062-2 | doi-access = free }}</ref>

[[Image:Schematic representation of Treg-related TRACs identified by RNAseq.jpg|thumb|300px|Transcripts associated with CAD identified by [[RNA-seq]]. The differentially expressed genes identified by RNAseq were curated by automated and manual analysis to identify the molecular pathways involved. The resulting pattern points to changes in the 'immune synapse', which involves both endocytic pathways of T cell receptor-containing vesicles, as well as ciliary protrusions that couple to intracellular signaling pathways.]]

The RNA changes are mostly related to ciliary and endocytic transcripts, which in the circulating immune system would be related to the [[immune synapse]].<ref>{{cite journal | vauthors = McCaffrey TA, Toma I, Yang Z, Katz R, Reiner J, Mazhari R, Shah P, Falk Z, Wargowsky R, Goldman J, Jones D, Shtokalo D, Antonets D, Tisha Jepson T, Fetisova A, Jaatinen K, Ree N, Ri M| title = RNAseq profiling of blood from patients with coronary artery disease: Signature of a T cell imbalance | journal = Journal of Molecular and Cellular Cardiology Plus | volume = 4 | date = June 2023 | page = 100033 | doi = 10.1016/j.jmccpl.2023.100033| pmid = 37303712 | pmc = 10256136 | s2cid = 257761467 }}</ref> One of the most differentially expressed genes, [[fibromodulin]] (FMOD), which is increased 2.8-fold in CAD, is found mainly in connective tissue<ref>{{cite journal | pmc=9986681 | date=2023 | title=Fibromodulin, a Multifunctional Matricellular Modulator | journal=Journal of Dental Research | volume=102 | issue=2 | pages=125–34 | doi=10.1177/00220345221138525 | pmid=36515321 | vauthors = Zheng Z, Granado HS, Li C }}</ref> and is a modulator of the TGF-beta signaling pathway. However, not all RNA changes may be related to the immune synapse. For example, [[Nebulette]], the most down-regulated transcript (2.4-fold), is found in cardiac muscle; it is a 'cytolinker' that connects actin and desmin to facilitate cytoskeletal function and vesicular movement. The endocytic pathway is further modulated by changes in [[tubulin]], a key microtubule protein, and [[fidgetin]], a tubulin-severing enzyme that is a marker for cardiovascular risk identified by [[genome-wide association study]]. Protein recycling would be modulated by changes in the proteasomal regulator [[SIAH3]], and the ubiquitin ligase [[MARCHF10]]. On the ciliary aspect of the immune synapse, several of the modulated transcripts are related to ciliary length and function. [[STRC|Stereocilin]] is a partner to [[mesothelin]], a related [[superhelix|super-helical]] protein, whose transcript is also modulated in CAD. [[DCDC2]], a double-cortin protein, modulates ciliary length. In the signaling pathways of the immune synapse, numerous transcripts are directly related to T-cell function and the control of differentiation. [[Butyrophilin]] is a co-regulator for T cell activation. [[Fibromodulin]] modulates the TGF-beta signaling pathway, a primary determinant of Tre differentiation. Further impact on the [[TGF-beta]] pathway is reflected in concurrent changes in the BMP receptor 1B RNA (BMPR1B), because the bone morphogenic proteins are members of the TGF-beta superfamily, and likewise impact Treg differentiation. Several of the transcripts ([[TMEM98]], [[NRCAM]], [[SFRP5]], [[SHISA2]]) are elements of the Wnt signaling pathway, which is a major determinant of Treg differentiation.