ArticleCirculation2012
Role for substance p-based nociceptive signaling in progenitor cell activation and angiogenesis during ischemia in mice and in human subjects.
Article in Circulation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 106 citations in OpenAlex.
- Autologous peripheral blood-derived stem cells transplantation for treatment of no-option angiitis-induced critical limb ischemia: 10-year management experience.Stem cell research & therapy · 2020Trial
- Trial
- The immediate effect of traditional Malay massage on substance P, inflammatory mediators, pain scale and functional outcome among patients with low back pain: study protocol of a randomised controlled trial.BMC complementary and alternative medicine · 2016Trial
- Novel Noxipoint Therapy versus Conventional Physical Therapy for Chronic Neck and Shoulder Pain: Multicentre Randomised Controlled Trials.Scientific reports · 2015Trial
- The Broken Cradle: Bone Marrow Stem Cell Niche Remodelling in Diabetes.Stem cell reviews and reports · 2026Review
- Biomaterial-assisted neuralization strategies for tissue engineering applications.Materials today. Bio · 2026Review
- [Research progress on the role of peripheral nerves in wound healing].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
- Preliminary Investigation on Efficacy and Safety of Substance P-Coated Stent for Promoting Re-Endothelialization: A Porcine Coronary Artery Restenosis Model.Tissue engineering and regenerative medicine · 2024Article
- Bioactive materials forBioactive materials · 2024Review
- Endometriosis: Cellular and Molecular Mechanisms Leading to Fibrosis.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Bone marrow vasculature advancedFrontiers in cardiovascular medicine · 2023Review
- Substance P prevents doxorubicin‑induced cardiomyocyte injury by regulating apoptosis and autophagy:Molecular medicine reports · 2022Article
- A cohort study of circulating progenitor cells after ST-segment elevation and non-ST segment elevation myocardial infarction in non-diabetic and diabetic patients.Frontiers in cardiovascular medicine · 2022Article
- Nociception-Dependent CCL21 Induces Dorsal Root Ganglia Axonal GrowthFrontiers in immunology · 2022Article
- Cutaneous innervation in impaired diabetic wound healing.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Role of Glucose-Lowering Medications in Erectile Dysfunction.Journal of clinical medicine · 2021Review
- Cell Therapy for Critical Limb Ischemia: Advantages, Limitations, and New Perspectives for Treatment of Patients with Critical Diabetic Vasculopathy.Current diabetes reports · 2021Review
- When a Friend Becomes Your Enemy: Natural Killer Cells in Atherosclerosis and Atherosclerosis-Associated Risk Factors.Frontiers in immunology · 2021Review
- Activation of Bone Marrow Adaptive Immunity in Type 2 Diabetes: Rescue by Co-stimulation Modulator Abatacept.Frontiers in immunology · 2021Article
- Substance P enhances the local activation of NKBMC molecular and cell biology · 2020Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundPain triggers a homeostatic alarm reaction to injury. It remains unknown, however, whether nociceptive signaling activated by ischemia is relevant for progenitor cells (PC) release from bone marrow. To this end, we investigated the role of the neuropeptide substance P (SP) and cognate neurokinin 1 (NK1) nociceptor in PC activation and angiogenesis during ischemia in mice and in human subjects. METHODS AND
resultsThe mouse bone marrow contains sensory fibers and PC that express SP. Moreover, SP-induced migration provides enrichment for PC that express NK1 and promote reparative angiogenesis after transplantation in a mouse model of limb ischemia. Acute myocardial infarction and limb ischemia increase SP levels in peripheral blood, decrease SP levels in bone marrow, and stimulate the mobilization of NK1-expressing PC, with these effects being abrogated by systemic administration of the opioid receptor agonist morphine. Moreover, bone marrow reconstitution with NK1-knockout cells results in depressed PC mobilization, delayed blood flow recovery, and reduced neovascularization after ischemia. We next asked whether SP is instrumental to PC mobilization and homing in patients with ischemia. Human PC express NK1, and SP-induced migration provides enrichment for proangiogenic PC. Patients with acute myocardial infarction show high circulating levels of SP and NK1-positive cells that coexpress PC antigens, such as CD34, KDR, and CXCR4. Moreover, NK1-expressing PC are abundant in infarcted hearts but not in hearts that developed an infarct after transplantation.
conclusionsOur data highlight the role of SP in reparative neovascularization. Nociceptive signaling may represent a novel target of regenerative medicine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.