دورية أكاديمية
Ultrasound Neuromodulation of an Anti-Inflammatory Pathway at the Spleen Improves Experimental Pulmonary Hypertension.
| العنوان: | Ultrasound Neuromodulation of an Anti-Inflammatory Pathway at the Spleen Improves Experimental Pulmonary Hypertension. |
|---|---|
| المؤلفون: | Zafeiropoulos S; Elmezzi Graduate School of Molecular Medicine, Northwell Health, Manhasset, NY (S. Zafeiropoulos, A.B., Y.A.-A., G.G., S. Zanos).; Institute of Bioelectronic Medicine (S. Zafeiropoulos, U.A., A.B., N.J., I.T.M., N.S., A.D., Y.A.-A., S. Zanos), Feinstein Institutes for Medical Research, Manhasset, NY., Ahmed U; Department of Neurology, Staten Island University Hospital, Staten Island, NY (U.A.).; Institute of Bioelectronic Medicine (S. Zafeiropoulos, U.A., A.B., N.J., I.T.M., N.S., A.D., Y.A.-A., S. Zanos), Feinstein Institutes for Medical Research, Manhasset, NY., Bekiaridou A; Elmezzi Graduate School of Molecular Medicine, Northwell Health, Manhasset, NY (S. Zafeiropoulos, A.B., Y.A.-A., G.G., S. Zanos).; Institute of Bioelectronic Medicine (S. Zafeiropoulos, U.A., A.B., N.J., I.T.M., N.S., A.D., Y.A.-A., S. Zanos), Feinstein Institutes for Medical Research, Manhasset, NY., Jayaprakash N; Institute of Bioelectronic Medicine (S. Zafeiropoulos, U.A., A.B., N.J., I.T.M., N.S., A.D., Y.A.-A., S. Zanos), Feinstein Institutes for Medical Research, Manhasset, NY., Mughrabi IT; Institute of Bioelectronic Medicine (S. Zafeiropoulos, U.A., A.B., N.J., I.T.M., N.S., A.D., Y.A.-A., S. Zanos), Feinstein Institutes for Medical Research, Manhasset, NY., Saleknezhad N; Institute of Bioelectronic Medicine (S. Zafeiropoulos, U.A., A.B., N.J., I.T.M., N.S., A.D., Y.A.-A., S. Zanos), Feinstein Institutes for Medical Research, Manhasset, NY., Chadwick C; General Electric Global Research, Niskayuna, NY (C.C., C.P.)., Daytz A; Institute of Bioelectronic Medicine (S. Zafeiropoulos, U.A., A.B., N.J., I.T.M., N.S., A.D., Y.A.-A., S. Zanos), Feinstein Institutes for Medical Research, Manhasset, NY., Kurata-Sato I; Institute of Molecular Medicine (I.K.-S., Y.A.-F., K.C., B.D.), Feinstein Institutes for Medical Research, Manhasset, NY., Atish-Fregoso Y; Institute of Molecular Medicine (I.K.-S., Y.A.-F., K.C., B.D.), Feinstein Institutes for Medical Research, Manhasset, NY., Carroll K; Institute of Molecular Medicine (I.K.-S., Y.A.-F., K.C., B.D.), Feinstein Institutes for Medical Research, Manhasset, NY., Al-Abed Y; Elmezzi Graduate School of Molecular Medicine, Northwell Health, Manhasset, NY (S. Zafeiropoulos, A.B., Y.A.-A., G.G., S. Zanos).; Institute of Bioelectronic Medicine (S. Zafeiropoulos, U.A., A.B., N.J., I.T.M., N.S., A.D., Y.A.-A., S. Zanos), Feinstein Institutes for Medical Research, Manhasset, NY., Fudim M; Division of Cardiology, Duke University Medical Center, Durham, NC (M.F.).; Duke Clinical Research Institute, Durham, NC (M.F.)., Puleo C; General Electric Global Research, Niskayuna, NY (C.C., C.P.)., Giannakoulas G; Elmezzi Graduate School of Molecular Medicine, Northwell Health, Manhasset, NY (S. Zafeiropoulos, A.B., Y.A.-A., G.G., S. Zanos).; Department of Cardiology, AHEPA University Hospital, Aristotle University School of Medicine, Thessaloniki, Greece (G.G.)., Nicolls MR; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Stanford University, CA (M.R.N.)., Diamond B; Institute of Molecular Medicine (I.K.-S., Y.A.-F., K.C., B.D.), Feinstein Institutes for Medical Research, Manhasset, NY.; Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY (B.D., S. Zanos)., Zanos S; Elmezzi Graduate School of Molecular Medicine, Northwell Health, Manhasset, NY (S. Zafeiropoulos, A.B., Y.A.-A., G.G., S. Zanos).; Institute of Bioelectronic Medicine (S. Zafeiropoulos, U.A., A.B., N.J., I.T.M., N.S., A.D., Y.A.-A., S. Zanos), Feinstein Institutes for Medical Research, Manhasset, NY.; Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY (B.D., S. Zanos). |
| المصدر: | Circulation research [Circ Res] 2024 Jun 21; Vol. 135 (1), pp. 41-56. Date of Electronic Publication: 2024 May 07. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0047103 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4571 (Electronic) Linking ISSN: 00097330 NLM ISO Abbreviation: Circ Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, MD : Lippincott Williams & Wilkins Original Publication: Baltimore, Md. Grune & Stratton. |
| مواضيع طبية MeSH: | Spleen*/metabolism , Hypertension, Pulmonary*/therapy , Hypertension, Pulmonary*/metabolism, Animals ; Male ; Rats ; Rats, Sprague-Dawley ; Disease Models, Animal ; Ultrasonic Waves |
| مستخلص: | Background: Inflammation is pathogenically implicated in pulmonary arterial hypertension; however, it has not been adequately targeted therapeutically. We investigated whether neuromodulation of an anti-inflammatory neuroimmune pathway involving the splenic nerve using noninvasive, focused ultrasound stimulation of the spleen (sFUS) can improve experimental pulmonary hypertension. Methods: Pulmonary hypertension was induced in rats either by Sugen 5416 (20 mg/kg SQ) injection, followed by 21 (or 35) days of hypoxia (sugen/hypoxia model), or by monocrotaline (60 mg/kg IP) injection (monocrotaline model). Animals were randomized to receive either 12-minute-long sessions of sFUS daily or sham stimulation for 14 days. Catheterizations, echocardiography, indices of autonomic function, lung and heart histology and immunohistochemistry, spleen flow cytometry, and lung single-cell RNA sequencing were performed after treatment to assess the effects of sFUS. Results: Splenic denervation right before induction of pulmonary hypertension results in a more severe disease phenotype. In both sugen/hypoxia and monocrotaline models, sFUS treatment reduces right ventricular systolic pressure by 25% to 30% compared with sham treatment, without affecting systemic pressure, and improves right ventricular function and autonomic indices. sFUS reduces wall thickness, apoptosis, and proliferation in small pulmonary arterioles, suppresses CD3 + and CD68 + cell infiltration in lungs and right ventricular fibrosis and hypertrophy and lowers BNP (brain natriuretic peptide). Beneficial effects persist for weeks after sFUS discontinuation and are more robust with early and longer treatment. Splenic denervation abolishes sFUS therapeutic benefits. sFUS partially normalizes CD68 + and CD8 + T-cell counts in the spleen and downregulates several inflammatory genes and pathways in nonclassical and classical monocytes and macrophages in the lung. Differentially expressed genes in those cell types are significantly enriched for human pulmonary arterial hypertension-associated genes. Conclusions: sFUS causes dose-dependent, sustained improvement of hemodynamic, autonomic, laboratory, and pathological manifestations in 2 models of experimental pulmonary hypertension. Mechanistically, sFUS normalizes immune cell populations in the spleen and downregulates inflammatory genes and pathways in the lung, many of which are relevant in human disease. Competing Interests: Disclosures None. |
| التعليقات: | Comment in: Circ Res. 2024 Jun 21;135(1):57-59. doi: 10.1161/CIRCRESAHA.124.324791. (PMID: 38900858) |
| فهرسة مساهمة: | Keywords: apoptosis; cell proliferation; fibrosis; hypertension, pulmonary; hypoxia; macrophages |
| تواريخ الأحداث: | Date Created: 20240507 Date Completed: 20240620 Latest Revision: 20240620 |
| رمز التحديث: | 20240621 |
| DOI: | 10.1161/CIRCRESAHA.123.323679 |
| PMID: | 38712557 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1524-4571 |
|---|---|
| DOI: | 10.1161/CIRCRESAHA.123.323679 |