W2 Professorship for Experimental Vascular Medicine
Research Group Leader
- Prof. Dr. med. Florian P. Limbourg
Research Assistants
- Jaba Gamrekelashvili, PhD
- Dr. rer. nat. Tamar Kapanadze
- Dr. med. Christian Beger
- Dr. med. Khaled Dastagir
- Nicole Schroth
- Yuangao Xu
- Theresa Karg
- Carla Schulze
Technical Assistants
- Stefan Sablotny
Scientific profile
In the laboratory, we are investigating the fundamentals of the development and regulation of the inflammatory response in cardiovascular diseases, and in clinical studies, new diagnostic and management concepts for patients with art. Hypertension (high blood pressure).
Organ or tissue damage causes an inflammatory response (inflammation) that aims to promote tissue healing and restore organ function. However, the inflammatory response is too often uncontrolled, amplifying disease processes. We have shown that blood vessels influence the cell fate of monocytes and macrophages through cell-cell communication, directly influencing the inflammatory response at the site. Different endothelial cell populations express Notch ligands of the delta-like (Dll) family in specialized niches, which in turn activates Notch signaling in monocytes and controls homeostatic differentiation of monocytes. The same process also promotes monocyte maturation into healing macrophages after ischemia, whereas targeted deletion of the ligand in endothelial cells impairs normal monocyte differentiation, leading to increased inflammation and impairing vascular regeneration after ischemia. In recent work, we further demonstrated that vascular endothelium regulates the formation of tertiary lymphoid structures, de novo immune centers in solid organs. This work has opened a new aspect of the concept of endothelial dysfunction and revealed another important function of blood vessels independent of blood flow.
In a current clinical trial of the Hypertension Center, we are testing the use of a blood pressure app for app-based self-management of hypertension in collaboration with primary care physicians. In a clinical registry study, we are testing novel and simplified algorithms for the work-up of patients with refractory hypertension.
Selected publications
Richter B*, Kapanadze T*, Weingärtner N, Walter S, Vogt I, Grund A, Schmitz J,
Bräsen JH, Limbourg FP, Haffner D, Leifheit-Nestler M. High phosphate-induced
progressive proximal tubular injury is associated with the activation of
Stat3/Kim-1 signaling pathway and macrophage recruitment. FASEB J. 2022
Jul;36(7):e22407. doi: 10.1096/fj.202200167RR. PMID: 35713543.
Fleig S, Kapanadze T, Bernier-Latmani J, Lill JK, Wyss T, Gamrekelashvili J,
Kijas D, Liu B, Hüsing AM, Bovay E, Jirmo AC, Halle S, Ricke-Hoch M, Adams RH,
Engel DR, von Vietinghoff S, Förster R, Hilfiker-Kleiner D, Haller H, Petrova
TV, Limbourg FP. Loss of vascular endothelial notch signaling promotes
spontaneous formation of tertiary lymphoid structures. Nat Commun. 2022 Apr
19;13(1):2022. doi: 10.1038/s41467-022-29701-x. PMID: 35440634; PMCID:
PMC9018798.
Gamrekelashvili J, Haller H, Limbourg FP. Analysis of Monocyte Cell Fate by
Adoptive Transfer in a Murine Model of TLR7-induced Systemic Inflammation. Bio
Protoc. 2021 May 5;11(9):e4007. doi: 10.21769/BioProtoc.4007. PMID: 34124307;
PMCID: PMC8161141.
Gamrekelashvili J, Kapanadze T, Sablotny S, Ratiu C, Dastagir K, Lochner M,
Karbach S, Wenzel P, Sitnow A, Fleig S, Sparwasser T, Kalinke U, Holzmann B,
Haller H, Limbourg FP. Notch and TLR signaling coordinate monocyte cell fate and
inflammation. Elife. 2020 Jul 29;9:e57007. doi: 10.7554/eLife.57007. PMID:
32723480; PMCID: PMC7413669.
Beger C, Unger T, Haller H, Limbourg FP. Antihypertensive prescription
patterns and cardiovascular risk in patients with newly diagnosed hypertension-
an analysis of statutory health insurance data in Germany. Blood Press. 2020
Dec;29(6):357-361. doi: 10.1080/08037051.2020.1779582. Epub 2020 Jun 16. PMID:
32543915.
Haupt F, Krishnasamy K, Napp LC, Augustynik M, Limbourg A, Gamrekelashvili J,
Bauersachs J, Haller H, Limbourg FP. Retinal myeloid cells regulate tip cell
selection and vascular branching morphogenesis via Notch ligand Delta-like 1.
Sci Rep. 2019 Jul 5;9(1):9798. doi: 10.1038/s41598-019-46308-3. PMID: 31278348;
PMCID: PMC6611798.
Kapanadze T, Bankstahl JP, Wittneben A, Koestner W, Ballmaier M,
Gamrekelashvili J, Krishnasamy K, Limbourg A, Ross TL, Meyer GJ, Haller H,
Bengel FM, Limbourg FP. Multimodal and Multiscale Analysis Reveals Distinct
Vascular, Metabolic and Inflammatory Components of the Tissue Response to Limb
Ischemia. Theranostics. 2019 Jan 1;9(1):152-166. doi: 10.7150/thno.27175. PMID:
30662559; PMCID: PMC6332799.
Getzin T, Krishnasamy K, Gamrekelashvili J, Kapanadze T, Limbourg A, Häger C,
Napp LC, Bauersachs J, Haller H, Limbourg FP. The chemokine receptor
CX3CR1 coordinates monocyte recruitment and endothelial regeneration
after arterial injury. EMBO Mol Med. 2018 Feb;10(2):151-159. doi:
10.15252/emmm.201707502. PMID: 29229785; PMCID: PMC5801509.
Krishnasamy K, Limbourg A, Kapanadze T, Gamrekelashvili J, Beger C, Häger C,
Lozanovski VJ, Falk CS, Napp LC, Bauersachs J, Mack M, Haller H, Weber C, Adams
RH, Limbourg FP. Blood vessel control of macrophage maturation promotes
arteriogenesis in ischemia. Nat Commun. 2017 Oct 16;8(1):952. doi:
10.1038/s41467-017-00953-2. PMID: 29038527; PMCID: PMC5643305.
Gamrekelashvili J, Giagnorio R, Jussofie J, Soehnlein O, Duchene J, Briseño
CG, Ramasamy SK, Krishnasamy K, Limbourg A, Kapanadze T, Ishifune C, Hinkel R,
Radtke F, Strobl LJ, Zimber-Strobl U, Napp LC, Bauersachs J, Haller H, Yasutomo
K, Kupatt C, Murphy KM, Adams RH, Weber C, Limbourg FP. Regulation of monocyte
cell fate by blood vessels mediated by Notch signalling. Nat Commun. 2016 Aug
31;7:12597. doi: 10.1038/ncomms12597. Erratum in: Nat Commun. 2017 May
03;8:15486. PMID: 27576369; PMCID: PMC5013671.
Current third-party funding
Regulation of monocyte lineage development in systemic and vascular inflammation and
the influence of Notch signaling
Sponsor: Deutsche Forschungsgemeinschaft
PI: Gamrekelashvili GA 2443/3-1, 2021-24
Monozyten-Differenzierung in der ischämischen Knochenmarknische bei Extremitätenischämie und Regulation durch die Notch Signaltransduktion
Sponsor: Deutsche Forschungsgemeinschaft
PI: Kapanadze KA 5549/2-1, 2021-24
Topographie der vaskulären Nische bei Ischämie
Sponsor: Deutsche Forschungsgemeinschaft
PI: Limbourg Li948/7-1, 2018-2022
PRACTIS
Sponsor MHH/ Deutsche Forschungsgemeinschaft
PI: Dastagir, 2019-21
Regulation of monocyte cell fate by blood vessels through Notch signaling and significance for vascular repair
Sponsor: Deutsche Forschungsgemeinschaft
PI: Gamrekelashvili Ga2443/2-1, 2017-2020
Junge Akademie / Clinical Scientist Programm
Sponsor: MHH/ Deutsche Forschungsgemeinschaft
PI: Fleig, 2017-19
Patrolling monocytes in endothelial function and molecular regulation
Sponsor: Deutsche Stiftung für Herzforschung
PI: Gamrekelashvili/Limbourg, 2015-16
Open positions and PhD projects
n.a.
Contact
E-Mail limbourg.florian(at)mh-hannover.de