Brian Ruhle, MD, MS

All Publications

• Preoperative Weight Loss with Glucagon-Like Peptide-1 Receptor Agonists Before Bariatric Surgery Ruhle, B., Bartoletti, S., Hauser, M., Azagury, D. E. LIPPINCOTT WILLIAMS & WILKINS. 2023: S28

  View details for Web of Science ID 001094086300029

• Germ line predisposition variants occur in myelodysplastic syndrome patients of all ages. Blood Feurstein, S., Trottier, A. M., Estrada-Merly, N., Pozsgai, M., McNeely, K., Drazer, M. W., Ruhle, B., Sadera, K., Koppayi, A. L., Scott, B. L., Oran, B., Nishihori, T., Agrawal, V., Saad, A., Lindsley, R. C., Nakamura, R., Kim, S., Hu, Z., Sobecks, R., Spellman, S., Saber, W., Godley, L. A. 2022; 140 (24): 2533-2548

  Abstract

  The frequency of pathogenic/likely pathogenic (P/LP) germ line variants in patients with myelodysplastic syndrome (MDS) diagnosed at age 40 years or less is 15% to 20%. However, there are no comprehensive studies assessing the frequency of such variants across the age spectrum. We performed augmented whole-exome sequencing of peripheral blood samples from 404 patients with MDS and their related donors before allogeneic hematopoietic stem cell transplantation. Single-nucleotide and copy number variants in 233 genes were analyzed and interpreted. Germ line status was established by the presence of a variant in the patient and related donor or for those seen previously only as germ line alleles. We identified P/LP germ line variants in 28 of 404 patients with MDS (7%), present within all age deciles. Patients with P/LP variants were more likely to develop higher-grade MDS than those without (43% vs 25%; P = .04). There was no statistically significant difference in outcome parameters between patients with and without a germ line variant, but the analysis was underpowered. P/LP variants in bone marrow failure syndrome genes were found in 5 patients aged less than 40 years, whereas variants in DDX41 (n = 4), telomere biology disorder genes (n = 2), and general tumor predisposition genes (n = 17) were found in patients aged more than 40 years. If presumed germ line variants were included, the yield of P/LP variants would increase to 11%, and by adding suspicious variants of unknown significance, it would rise further to 12%. The high frequency of P/LP germ line variants in our study supports comprehensive germ line genetic testing for all patients with MDS regardless of their age at diagnosis.

  View details for DOI 10.1182/blood.2022015790

  View details for PubMedID 35969835

  View details for PubMedCentralID PMC9918848

• Autologous Posterior Rectus Sheath as a Vascularized Onlay Flap: a Novel Approach to Hiatal Hernia Repair. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Vigneswaran, Y., Bryan, A. F., Ruhle, B., Gottlieb, L. J., Alverdy, J. 2022; 26 (1): 268-274

  Abstract

  Complex and recurrent paraesophageal hernia repairs are a challenge for surgeons due to their high recurrence rates despite the use of various prosthetic and suturing techniques.Here we describe the use of vascularized fascia harvested from the posterior rectus sheath with peritoneum during robotic hiatal hernia repair in two patients with large complex diaphragmatic defects.Successful harvesting and onlay of the right posterior rectus sheath based on a falciform vascular pedicle was achieved robotically by rotating and securing the flap to the diaphragmatic hiatus as an onlay flap following cruroplasty of the hiatal defect.In patients with difficult to repair large paraesophageal hernias, we demonstrate a promising new technique to restore the dynamic hiatal complex with the tensile strength of autologous vascularized fascia and peritoneum.

  View details for DOI 10.1007/s11605-021-05134-7

  View details for PubMedID 34506032

  View details for PubMedCentralID PMC8760196

• Total Thyroidectomy vs Thyroid Lobectomy for Localized Papillary Thyroid Cancer in Children: A Propensity-Matched Survival Analysis. Journal of the American College of Surgeons Memeh, K., Ruhle, B., Alsafran, S., Vaghaiwalla, T., Kaplan, E., Angelos, P., Keutgen, X. M. 2021; 233 (1): 39-49

  Abstract

  Current guidelines recommend total thyroidectomy (TT) and radioablation for most papillary thyroid cancer (PTC) in children. These guidelines have been criticized as aggressive, especially for early-stage PTC, as it likely does not influence patient survival and results in life-long thyroid hormone replacement. We sought to study whether the extent of thyroidectomy (TT vs thyroid lobectomy [TL]) influences overall and disease-specific survival in children with localized PTC.The National Cancer Database and the Surveillance, Epidemiology, and End Results registries were queried. Patients 18 years or younger with low-risk PTC between 2004 and 2016 were included. Using a 1:1 propensity score matching, patients who underwent TT were matched for age, sex, race, year of diagnosis, and tumor size with a similar cohort of patients who underwent TL. Primary end points were overall survival and disease-specific survival.There were 3,500 patients identified as surgically treated for PTC, of which 1,325 patients met inclusion criteria for matching. Three hundred and twenty-six patients were matched. One hundred and sixty-three patients had TT; 140 were female and mean age was 16 years (interquartile range [IQR] 13 to 17 years). One hundred and sixty-three patients had TL; 140 were female and mean age was 16 years (IQR 14 to 17 years). Median follow-up was 5.0 years (IQR 2.8 to 8 years) and 8.3 years (IQR 3.6 to 14.4 years) in the National Cancer Database and Surveillance, Epidemiology, and End Results cohorts, respectively. There was no statistically significant difference in overall survival or disease-specific survival in patients with PTC < 4 cm, regardless of whether patients underwent TT or TL (p = 0.32 for National Cancer Database registry and p = 0.67 for Surveillance, Epidemiology, and End Results registry).This study suggests that the extent of thyroidectomy does not influence survival for pediatric patients with early-stage PTC and that TL might be adequate in this patient population.

  View details for DOI 10.1016/j.jamcollsurg.2021.03.025

  View details for PubMedID 33887483

• Response Rates in Metastatic Neuroendocrine Tumors Receiving Peptide Receptor Radionuclide Therapy and Implications for Future Treatment Strategies Vaghaiwalla, T., Ruhle, B., Memeh, K., Angelos, P., Kaplan, E., Polite, B., Liao, C., Keutgen, X. LIPPINCOTT WILLIAMS & WILKINS. 2021: 457

  View details for Web of Science ID 000655285500095

• Thyroidectomy for euthyroid patients with Hashimoto thyroiditis and persisting symptoms: A cost-effectiveness analysis. Surgery Memeh, K., Ruhle, B., Vaghaiwalla, T., Kaplan, E., Keutgen, X., Angelos, P. 2021; 169 (1): 7-13

  Abstract

  Despite thyroid hormone replacement, some euthyroid patients with Hashimoto thyroiditis will continue to experience persistent symptoms that reduce their quality of life. Recent studies indicate that total thyroidectomy is superior to medical therapy alone in improving these symptoms. However, there is a high complication rate after total thyroidectomy in patients with Hashimoto thyroiditis. This study evaluates the cost-effectiveness of total thyroidectomy for euthyroid patients who have Hashimoto thyroiditis with persistent symptoms.We utilized a Markov model to compare total thyroidectomy and medical therapy alone over the lifetime of the cohort. Costs, probabilities, and utility parameters were derived from literature and Medicare cost data. A willingness-to-pay threshold of $100,000/quality-adjusted life years was used. We performed sensitivity analyses to ascertain model uncertainty.On average, medical therapy alone costs $12,845, produced 16.9 quality-adjusted life years, and was dominated. Total thyroidectomy costs $1,490 less and produced 1.4 more quality-adjusted life years. Probabilistic sensitivity analysis confirmed total thyroidectomy as the optimal strategy in 89% of cases. Medical therapy alone will become cost-effective if the cost of uncomplicated thyroidectomy increases by 25%, if the probability of permanent complication after total thyroidectomy increases 12-fold, or if there is no gain in quality of life after thyroidectomy.Total thyroidectomy is more cost-effective than medical therapy alone for the management of euthyroid patients who have Hashimoto thyroiditis with persistent symptoms.

  View details for DOI 10.1016/j.surg.2020.03.028

  View details for PubMedID 32460999

• Robot-Assisted Endocrine Surgery: Indications and Drawbacks. Journal of laparoendoscopic & advanced surgical techniques. Part A Ruhle, B. C., Ferguson Bryan, A., Grogan, R. H. 2019; 29 (2): 129-135

  Abstract

  Over the last few decades, robotic surgery with the da Vinci system has become increasingly prevalent. Endocrine surgeons are witnessing a rapid growth in enthusiasm for robotic approaches for treating thyroid, parathyroid, and adrenal disease. For carefully selected patients, the robotic system may be the preferred technique, although its use remains controversial and indications are in evolution. The goal of this article is to review current robotic procedures for thyroidectomy, parathyroidectomy, and adrenalectomy, and scrutinize the existing literature for application of these approaches.We systematically searched and reviewed relevant articles on PubMed and MEDLINE databases for robotic or robot-assisted thyroidectomy, parathyroidectomy, or adrenalectomy.The safety and feasibility for robotic thyroidectomy, parathyroidectomy, and adrenalectomy have been repeatedly demonstrated. Although robotic thyroid and parathyroid surgery offers better cosmetic results compared to the conventional open operation, remote-access techniques introduce new risks. Similar outcomes have been reported for laparoscopic and robotic adrenalectomy, but robot-assisted techniques may extend the capabilities of minimally invasive surgery, particularly performing subtotal adrenalectomy.While robotic procedures offer better ergonomics for the endocrine surgeon and improved cosmesis for the patient, the major drawback to the robot system almost universally is the higher cost. With new robotically assisted surgical devices on the way that could drive down costs and speed up innovation, the indications for robotic endocrine surgery may greatly expand.

  View details for DOI 10.1089/lap.2018.0308

  View details for PubMedID 30133339

• Keeping primary aldosteronism in mind: Deficiencies in screening at-risk hypertensives. Surgery Ruhle, B. C., White, M. G., Alsafran, S., Kaplan, E. L., Angelos, P., Grogan, R. H. 2019; 165 (1): 221-227

  Abstract

  Primary aldosteronism is a common but underdiagnosed cause of hypertension. Patients with this disorder have worse morbidity compared with those with essential hypertension, but with timely diagnosis and appropriate intervention these patients are potentially cured and may have reversal of target organ damage. The goal of this study was to determine if hypertensive patients considered high risk were checked for primary aldosteronism.We reviewed electronic health records to identify patients age 18 years or older with coexisting hypertension and hypokalemia or hypertension and sleep apnea, then determined if they had been investigated with measurement of aldosterone or renin. We built regression models to identify explanatory variables for screening in these 2 high-risk groups.Of nearly 37,000 patients with hypertension and hypokalemia, only 2.7% were ever screened for primary aldosteronism. Most opportunities for case detection were during inpatient hospitalizations, yet in this setting, patients were less likely than clinic patients be screened. Similarly, 3.0% of hypertensive patients with sleep apnea were screened since the inclusion of this group in case detection recommendations.Uptake of practice guidelines by hospital physicians, fueled by support from their specialty societies, may help to identify many more patients with unrecognized primary aldosteronism.

  View details for DOI 10.1016/j.surg.2018.05.085

  View details for PubMedID 30415872

• Preoperative calcitriol reduces postoperative intravenous calcium requirements and length of stay in parathyroidectomy for renal-origin hyperparathyroidism. Surgery Alsafran, S., Sherman, S. K., Dahdaleh, F. S., Ruhle, B., Mercier, F., Kaplan, E. L., Angelos, P., Grogan, R. H. 2019; 165 (1): 151-157

  Abstract

  Patients undergoing subtotal parathyroidectomy for renal-origin hyperparathyroidism often develop postoperative hypocalcemia, requiring calcitriol and intravenous calcium (Postop-IVCa). We hypothesized that in subtotal parathyroidectomy for renal-origin hyperparathyroidism, preoperative calcitriol treatment reduces the use of postoperative administration of intravenous calcium.A retrospective chart review compared subtotal parathyroidectomy for renal-origin hyperparathyroidism patients who received preoperative calcitriol treatment with those patietns who did not receive preoperative calcitriol treatment at one institution. Preoperative calcitriol treatment loading doses were 0.5 mcg twice daily for 5 days. All patients received postoperative calcitriol and oral calcium carbonate. Postoperative administration of intravenous calcium was given for symptoms, calcium <7.0 mg/dL, or surgeon preference. The Fisher exact test was used to compare proportions. The Wilcoxon test was used to compare continuous data. Multivariable logistic regression adjusted for confounders.Included were 81 patients who received subtotal parathyroidectomy for renal-origin hyperparathyroidism (41 patients who received preoperative calcitriol treatment, 40 patients who did not receive preoperative calcitriol treatment). Preoperative calcitriol treatment use increased over time (0% 2004-2010, 69% 2011-2016). Groups who received preoperative calcitriol treatment and groups who did not receive preoperative calcitriol treatment were similar in preoperative serum calcium, vitamin D, parathyroid hormone, and median age (P > .05 for all). Patients who received preoperative calcitriol treatment less often required postoperative administration of intravenous calcium (34% vs 90% of patients who did not receive preoperative calcitriol treatment, P < .001). Median length of stay was 2.0 days shorter for patients who received preoperative calcitriol treatment versus patients who did not receive preoperative calcitriol treatment patients (P < .001). Factors associated with postoperative administration of intravenous calcium included not receiving preoperative calcitriol treatment, low preoperative calcium, and high preoperative parathyroid hormone. After multivariable adjustment, preoperative calcitriol treatment remained independently associated with reduced postoperative administration of intravenous calcium (OR 0.02, P < .001).Preoperative calcitriol therapy lowered use of postoperative administration of intravenous calcium by 56% and length of stay by 50% in subtotal parathyroidectomy for renal-origin hyperparathyroidism patients. We believe preoperative calcitriol treatment should become standard of care for subtotal parathyroidectomy for renal-origin hyperparathyroidism.

  View details for DOI 10.1016/j.surg.2018.03.029

  View details for PubMedID 30413326

• Thrombospondin-1 differentially regulates microRNAs in vascular smooth muscle cells. Molecular and cellular biochemistry Maier, K. G., Ruhle, B., Stein, J. J., Gentile, K. L., Middleton, F. A., Gahtan, V. 2016; 412 (1-2): 111-7

  Abstract

  Thrombospondin-1 (TSP-1) is an important regulator of vascular smooth muscle cell (VSMC) physiology and gene expression. MicroRNAs (microRNA), small molecules that regulate protein translation, have emerged as potent regulators of cell function. MicroRNAs have been shown to be involved in intimal hyperplasia, atherosclerosis, and upregulated in the vasculature in diabetes. The purpose of this study was to identify microRNAs regulated by TSP-1 in vascular smooth muscle cells (VSMCs). Human VSMCs were treated for 6 h with basal media or TSP-1 both supplemented with 0.2% FBS. Cells were then snap frozen and RNA extracted. An Affymetrix GeneChip microRNA array analysis was performed in triplicate on three separate collections. Confirmatory qrtPCR was performed. Data were analyzed by ANOVA or t test, with significance set at p < 0.05. MicroRNAs identified were subjected to KEGG pathway analysis using the DIANA tools miRPath online tool. TSP-1 upregulated 22 microRNAs and downregulated 18 microRNAs in VSMCs (p < 0.05). The most upregulated microRNA was miR-512-3p (45.12 fold). The microRNA most downregulated by TSP-1 was miR-25-5p, which was decreased by 9.61. Of note, five members of the mir-17-92 cluster were downregulated. KEGG analysis revealed that thirty-three cellular signaling pathways were impacted by these microRNAs and that nine pathways were relevant to vascular disease. MicroRNAs regulate protein expression at the level of translation and may represent a significant mechanism by which TSP-1 regulates VSMC function. Several of the microRNAs identified have a role in vascular function. The miR-17-92 cluster family, which was found to exhibit reduced expression in this study, is known to be involved in angiogenesis and vascular function. TSP-1 regulates multiple microRNAs in VSMCs adding a new layer of complexity to TSP-1 regulation of VSMC function.

  View details for DOI 10.1007/s11010-015-2614-9

  View details for PubMedID 26728995

• Specific ion effects on macromolecular interactions in Escherichia coli extracts. Protein science : a publication of the Protein Society Kyne, C., Ruhle, B., Gautier, V. W., Crowley, P. B. 2015; 24 (3): 310-8

  Abstract

  Protein characterization in situ remains a major challenge for protein science. Here, the interactions of ΔTat-GB1 in Escherichia coli cell extracts were investigated by NMR spectroscopy and size exclusion chromatography (SEC). ΔTat-GB1 was found to participate in high molecular weight complexes that remain intact at physiologically-relevant ionic strength. This observation helps to explain why ΔTat-GB1 was not detected by in-cell NMR spectroscopy. Extracts pre-treated with RNase A had a different SEC elution profile indicating that ΔTat-GB1 predominantly interacted with RNA. The roles of biological and laboratory ions in mediating macromolecular interactions were studied. Interestingly, the interactions of ΔTat-GB1 could be disrupted by biologically-relevant multivalent ions. The most effective shielding of interactions occurred in Mg(2+) -containing buffers. Moreover, a combination of RNA digestion and Mg(2+) greatly enhanced the NMR detection of ΔTat-GB1 in cell extracts.

  View details for DOI 10.1002/pro.2615

  View details for PubMedID 25492389

  View details for PubMedCentralID PMC4353357

• Accuracy of NaF PET/CT scan to detect bone metastases in CRPC Alom, M., Aleksic, I., Ruhle, B., Iannotta, P., Okeefe, C., Mouraviev, V., Albala, D., Pieczonka, C. AMER SOC CLINICAL ONCOLOGY. 2014

  View details for DOI 10.1200/jco.2014.32.4_suppl.186

  View details for Web of Science ID 000335318100189

• Mechanisms of STIM1 activation of store-independent leukotriene C4-regulated Ca2+ channels. Molecular and cellular biology Zhang, X., González-Cobos, J. C., Schindl, R., Muik, M., Ruhle, B., Motiani, R. K., Bisaillon, J. M., Zhang, W., Fahrner, M., Barroso, M., Matrougui, K., Romanin, C., Trebak, M. 2013; 33 (18): 3715-23

  Abstract

  We recently showed, in primary vascular smooth muscle cells (VSMCs), that the platelet-derived growth factor activates canonical store-operated Ca(2+) entry and Ca(2+) release-activated Ca(2+) currents encoded by Orai1 and STIM1 genes. However, thrombin activates store-independent Ca(2+) selective channels contributed by both Orai3 and Orai1. These store-independent Orai3/Orai1 channels are gated by cytosolic leukotriene C4 (LTC4) and require STIM1 downstream LTC4 action. However, the source of LTC4 and the signaling mechanisms of STIM1 in the activation of this LTC4-regulated Ca(2+) (LRC) channel are unknown. Here, we show that upon thrombin stimulation, LTC4 is produced through the sequential activities of phospholipase C, diacylglycerol lipase, 5-lipo-oxygenease, and leukotriene C4 synthase. We show that the endoplasmic reticulum-resident STIM1 is necessary and sufficient for LRC channel activation by thrombin. STIM1 does not form sustained puncta and does not colocalize with Orai1 either under basal conditions or in response to thrombin. However, STIM1 is precoupled to Orai3 and Orai3/Orai1 channels under basal conditions as shown using Forster resonance energy transfer (FRET) imaging. The second coiled-coil domain of STIM1 is required for coupling to either Orai3 or Orai3/Orai1 channels and for LRC channel activation. We conclude that STIM1 employs distinct mechanisms in the activation of store-dependent and store-independent Ca(2+) entry pathways.

  View details for DOI 10.1128/MCB.00554-13

  View details for PubMedID 23878392

  View details for PubMedCentralID PMC3753864

• Emerging roles for native Orai Ca2+ channels in cardiovascular disease. Current topics in membranes Ruhle, B., Trebak, M. 2013; 71: 209-35

  Abstract

  Orai proteins form highly calcium (Ca(2+))-selective channels located in the plasma membrane of both nonexcitable and excitable cells, where they make important contributions to many cellular processes. The well-characterized Ca(2+) release-activated Ca(2+) current is mediated by Orai1 multimers and is activated, upon depletion of inositol 1,4,5-trisphosphate-sensitive stores, by direct interaction of Orai1 with the endoplasmic reticulum Ca(2+) sensor, stromal interaction molecule 1 (STIM1). This pathway is known as capacitative Ca(2+) entry or store-operated Ca(2+) entry. While most investigations have focused on STIM1 and Orai1 in their store-dependent mode, emerging evidence suggests that Orai1 and Orai3 heteromultimeric channels can form store-independent Ca(2+)-selective channels. The role of store-dependent and store-independent channels in excitation-transcription coupling and the pathological remodeling of the cardiovascular system are beginning to come forth. Recent evidence suggests that STIM/Orai-generated Ca(2+) signaling couples to gene transcription and subsequent phenotypic changes associated with the processes of cardiac and vascular remodeling. This short review will explore the contributions of native Orai channels to heart and vessel physiology and their role in cardiovascular diseases.

  View details for DOI 10.1016/B978-0-12-407870-3.00009-3

  View details for PubMedID 23890117

  View details for PubMedCentralID PMC5186411

• What role for store-operated Ca²⁺ entry in muscle? Microcirculation (New York, N.Y. : 1994) Trebak, M., Zhang, W., Ruhle, B., Henkel, M. M., González-Cobos, J. C., Motiani, R. K., Stolwijk, J. A., Newton, R. L., Zhang, X. 2013; 20 (4): 330-6

  Abstract

  Store-operated Ca²⁺ entry (SOCE) is a receptor-regulated Ca²⁺ entry pathway that is both ubiquitous and evolutionarily conserved. SOCE is activated by depletion of intracellular Ca²⁺ stores through receptor-mediated production of inositol 1,4,5-trisphosphate (IP₃). The depletion of endoplasmic reticulum (ER) Ca²⁺ is sensed by stromal interaction molecule 1 (STIM1). On store depletion, STIM1 aggregates and moves to areas where the ER comes close to the plasma membrane (PM; within 25 nm) to interact with Orai1 channels and activate Ca²⁺ entry. Ca²⁺ entry through store-operated Ca²⁺ (SOC) channels, originally thought to mediate the replenishment of Ca²⁺ stores, participate in active downstream signaling by coupling to the activation of enzymes and transcription factors that control a wide variety of long-term cell functions such as proliferation, growth, and migration. SOCE has also been proposed to contribute to short-term cellular responses such as muscle contractility. While there are significant STIM1/Orai1 protein levels and SOCE activity in adult skeletal muscle, the precise role of SOCE in skeletal muscle contractility is not clear. The dependence on SOCE during cardiac and smooth muscle contractility is even less certain. Here, we will hypothesize on the contribution of SOCE in muscle and its potential role in contractility and signaling.

  View details for DOI 10.1111/micc.12042

  View details for PubMedID 23312019

  View details for PubMedCentralID PMC3646967

• Store-independent Orai1/3 channels activated by intracrine leukotriene C4: role in neointimal hyperplasia. Circulation research González-Cobos, J. C., Zhang, X., Zhang, W., Ruhle, B., Motiani, R. K., Schindl, R., Muik, M., Spinelli, A. M., Bisaillon, J. M., Shinde, A. V., Fahrner, M., Singer, H. A., Matrougui, K., Barroso, M., Romanin, C., Trebak, M. 2013; 112 (7): 1013-25

  Abstract

  Through largely unknown mechanisms, Ca(2+) signaling plays important roles in vascular smooth muscle cell (VSMC) remodeling. Orai1-encoded store-operated Ca(2+) entry has recently emerged as an important player in VSMC remodeling. However, the role of the exclusively mammalian Orai3 protein in native VSMC Ca(2+) entry pathways, its upregulation during VSMC remodeling, and its contribution to neointima formation remain unknown.The goal of this study was to determine the agonist-evoked Ca(2+) entry pathway contributed by Orai3; Orai3 potential upregulation and role during neointima formation after balloon injury of rat carotid arteries.Ca(2+) imaging and patch-clamp recordings showed that although the platelet-derived growth factor activates the canonical Ca(2+) release-activated Ca(2+) channels via store depletion in VSMC, the pathophysiological agonist thrombin activates a distinct Ca(2+)-selective channel contributed by Orai1, Orai3, and stromal interacting molecule1 in the same cells. Unexpectedly, Ca(2+) store depletion is not required for activation of Orai1/3 channel by thrombin. Rather, the signal for Orai1/3 channel activation is cytosolic leukotrieneC4 produced downstream thrombin receptor stimulation through the catalytic activity of leukotrieneC4 synthase. Importantly, Orai3 is upregulated in an animal model of VSMC neointimal remodeling, and in vivo Orai3 knockdown inhibits neointima formation.These results demonstrate that distinct native Ca(2+)-selective Orai channels are activated by different agonists/pathways and uncover a mechanism whereby leukotrieneC4 acts through hitherto unknown intracrine mode to elicit store-independent Ca(2+) signaling that promotes vascular occlusive disease. Orai3 and Orai3-containing channels provide novel targets for control of VSMC remodeling during vascular injury or disease.

  View details for DOI 10.1161/CIRCRESAHA.111.300220

  View details for PubMedID 23349245

  View details for PubMedCentralID PMC3658112