Ablation of SAMD1 in Mice Causes Failure of Angiogenesis, Embryonic Lethality

Pathological retention of LDL in the intima is involved in atherosclerosis, although the retention mechanisms are not well-understood. Previously, we reported Sterile Alpha Motif Domain Containing 1 (SAMD1), a protein secreted by intimal smooth muscle cells in atherosclerotic lesions, appears to bind LDL in extracellular matrix around intimal cells. Fab-fragment inhibitors of apparently irreversible SAMD1/LDL binding reduced LDL retention in carotid injury models, but did not have a significant effect on early spontaneous lesion initiation. The normal function of SAMD1 is unknown, but it may have multiple epigenetic roles; our histology of mouse atherosclerosis models revealed extensive SAMD1 expression, possibly related to cell phenotype modulation and antigen presentation. For this report, we generated SAMD1-/-, SAMD1-/+, and SAMD1-/+ apoE-/- mice to further explore SAMD1's role in atherosclerosis. SAMD1 was found in tissues throughout the SAMD1+/+ and SAMD1-/+embryos. Homozygous loss of SAMD1 was embryonic lethal: at embryonic day 14, organs were partially developed and/or degraded; heads and brains were malformed; no blood vessels were observed; red blood cells were scattered and pooled, primarily near the embryo surface; and cell death was occurring. Development appeared normal in heterozygous SAMD1 embryos, but postnatal genotyping showed a reduced ability to thrive. Growth of atherosclerotic lesions in SAMD1-/+ apoE-/- after 35 weeks was not significantly less than in mice SAMD1+/+ apoE-/- mice.

Internal Carotid Injury during Transsphenoidal Resection of Pituitary Macroadenoma Managed with Neurointervention Technique

Iatrogenic internal carotid artery (ICA) injuries during transsphenoidal pituitary tumor surgery are extremely rare but are associated with potentially disabling or life-threatening complications. Management options of ICA injuries are sacrifice, embolization, and endoluminal reconstruction. We report a case of ICA injury during transsphenoidal pituitary macroadenoma surgery, which was managed with endovascular covered stent placement for left carotid-ophthalmic pseudoaneurysm.

Hyoid Elongation May Be a Rare Cause of Recurrent Ischemic Stroke in Youth-A Case Report and Literature Review

The investigation for etiology of ischemic stroke in young adults remains a diagnostic challenge. Hyoid bone–related carotid injury is a rare and under-recognized cause of ischemic stroke, without established guidelines. We describe a case of recurrent ischemic stroke in a young patient presumably attributed to an impingement of the carotid artery by an elongated hyoid bone, and present other cases reported in the literature. Based on the imaging study as well as the lack of other findings, we attributed recurrent neurovascular events to the repetitive mechanical stimulation by the elongated hyoid bone that caused a vessel wall injury with subsequent thrombus and embolus. Given repeated recurrence under antiplatelet treatment, anticoagulation was added. The following 2-year follow-up showed no new neurologic events or any other complaints. Among the young, a broad spectrum of possibilities should be considered and we call attention to this infrequent etiology of ischemic stroke.

Exosomal Transfer of miR-185 Is Controlled by hnRNPA2B1 and Impairs Re-endothelialization After Vascular Injury

Dysfunction of endothelial cells (ECs) contributes to restenosis after vascular reconstruction for patients with coronary artery disease (CAD). The intercellular communication between ECs and vascular smooth muscle cells (VSMCs) might be critical in the development of restenosis and can be mediated by exosomes carrying functional microRNAs. miR-185 is reported to be associated with atherosclerosis, whether it plays a similar role in restenosis is unknown. In this study, we observed an elevated level of extracellular miR-185 in platelet-derived growth factor (PDGF)-stimulated VSMCs. The medium from PDGF-stimulated VSMCs promoted miR-185 expression in rat aortic ECs and inhibited EC angiogenesis. PDGF-stimulated VSMCs transferred miR-185 into ECs via exosomes. Furthermore, we found that the CXCL12 gene, a target of miR-185, is essential for the angiogenic potential of ECs. Exosomes derived from miR-185 mimic transfected VSMCs attenuated re-endothelialization after vascular injury. Moreover, we show that exosome-mediated miR-185 transfer is modulated by hnRNPA2B1. We also observed that hnRNPA2B1 is up-regulated during neointima formation and hnRNPA2B1 inhibition accelerates re-endothelialization and attenuates neointima formation following carotid injury. Taken together, our results indicate that exosomal miR-185 transfer from VSMCs to ECs is controlled by hnRNPA2B1 and impairs re-endothelialization after vascular injury.

The Surgical Results in Pure Endoscopic Endonasal Trans-sphenoidal Surgeries in 403 Pituitary Adenomas: An 8-Years of Experience from a Single Neurosurgical Unit

Objective: To review and report the results in pure endoscopic endonasal trans-sphenoidal surgery done at our unit for pituitary adenomas (PAs) in last 8 years. Material and Methods: We reviewed 403 consecutive patients who underwent pure endoscopic endonasal trans-sphenoidal surgery for newly diagnosed pituitary adenomas between August 2012 and July 2020 at our neurosurgical unit. Endocrinological, demographic features and outcomes, their complications, and duration of stay in hospital were assessed in these patients who were operated in our neurosurgical Unit. The Mean Follow-up on average was 3.5 months. Results: 403 consecutive cases were reviewed. Majority of cases were in the 4th decade of life at presentation. 227 (56%) were non-functioning pituitary tumors and 176 (44%) were hormone secreting pituitary adenomas. Thirty-one (7.7%) complications were observed in 28 post-operative patients. The most frequently observed complication was diabetes insipidus (temporary in 19 (5%) and permanent in 3 (0.7%) cases), cerebrospinal fluids leaks (5 cases) (5.7%), Syndrome of inappropriate antidiuretic hormone (1 case) (0.2%), internal carotid injury (1 case) (0.2%), Empty Sella syndrome (1) (0.2%) and post-operative cardiac complication (1 case) (0.2%). The Follow-up on average was 3.5 months. Conclusions: The pure endoscopic endonasal trans-sphenoidal surgery of pituitary adenomas provides acceptable and reasonable results representing a safe alternative procedure to the traditional Trans-sphenoidal microscopic approach.