Project description:Transcriptional profiling of mouse aortas comparing control wild-type animals with aortas from three different Plk1(+/-) mice. Goal was to determine the effects of Plk1 haploinsufficiency in aorta expression profiles.
Project description:MicroRNAs (miRNAs) are short noncoding RNAs that impact protein expression, regulating a variety of physiological processes. To date, a few miRNAs have been implicated in the process of vascular calcification; however, our understanding of the miRNAs involved and their regulatory mechanisms remains incomplete.The analysis showed differences of microRNAs in the aortas after CKD induced vascular calcification.
Project description:To determine effects of hyperglycemia and insulin resistance on arterial wall biology, aortic gene expression profiles were generated using aortas from Lepr^db/db and their respective nondiabetic Lepr^db/+ controls. Keywords: Chip Experiment was done in triplicate with three independent pool of test Lepr^db/db and control Lepr^db/+ pooled samples. For RNA isolation aortas were striped of adventitia and periaortic fat. RNA from six aortas was pooled for the synthesis of probe for affymetrix array analysis.
Project description:To investigate the role of TET2 in osteogenic differentiation of smooth muscle cells (SMCs) in vivo, we performed single cell RNA-seq in cholecalciferol overload-induced calcified aortas of Tet2flox/flox and SMC specific Tet2 knock-out mice (Tet2SMC-KO).
Project description:B-cell leukemia 11b (BCL11B) is a transcription factor known as an essential regulator of T lymphocytes and neuronal development during embryogenesis. A genome-wide association study (GWAS) showed that a gene desert region downstream of BCL11B, known to function as a BCL11B enhancer, harbors single nucleotide polymorphisms (SNPs) associated with increased arterial stiffness. However, a role for BCL11B in the adult cardiovascular system is unknown. Based on these human findings, we sought to examine the relation between BCL11B and arterial function. Here we report that BCL11B is expressed in the vascular smooth muscle (VSM) where it regulates vascular stiffness. RNA sequencing of aortas from WT and Bcl11b null mice (BSMKO) identified the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) as the most significant differentially regulated signaling pathway in BSMKO compared to WT mice. BSMKO aortas showed decreased levels of PKG1, increased levels of Ca++-calmodulin-dependent serine/threonine phosphatase calcineurin (PP2B) and their common phosphorylation target, vasodilator-stimulated phosphoprotein (pVASPS239), a regulator of cytoskeletal actin rearrangements. Decreased pVASPS239 in BSMKO aortas was associated with increased actin polymerization (F/G actin ratio). Functionally, aortic force, stress, wall tension and stiffness, measured ex vivo in organ baths, were increased in BSMKO aortas, and BSMKO mice had increased pulse wave velocity, the in vivo index of arterial stiffness. Despite having no effect on blood pressure or microalbuminuria, increased arterial stiffness in BSMKO mice was associated with increased incidence of cerebral microbleeds compared to age-matched WT littermates. In conclusion, we have identified VSM BCL11B as a crucial regulator of aortic smooth muscle function and a potential therapeutic target for vascular stiffness.
