Biobanking: Objectives, Requirements, and Future Challenges—Experiences from the Munich Vascular Biobank

Pelisek, Jaroslav; Hegenloh, Renate; Bauer, Sabine; Metschl, Susanne; Pauli, Jessica; Glukha, Nadiya; Busch, Albert; Reutersberg, Benedikt; Kallmayer, Michael; Trenner, Matthias; Wendorff, Heiko; Tsantilas, Pavlos; Schmid, Sofie; Knappich, Christoph; Schaeffer, Christoph; Stadlbauer, Thomas; Bíró, G.; Wertern, Uta; Meisner, Franz; Stoklasa, Kerstin; Menges, Anna-Leonie; Radu, Oksana; Dallmann-Sieber, Sabine; Karlas, Angelos; Knipfer, Eva; Reeps, Christian; Zimmermann, Alexander; Maegdefessel, Lars; Eckstein, Hans‐Henning

doi:10.3390/jcm8020251

Cited by 38 publications

(28 citation statements)

References 53 publications

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“…Human abdominal aortic tissue specimens were provided by the Munich Vascular Biobank from patients undergoing elective open AAA repair and organ donors (kidney transplant surgery) [ 26 ]. Human ascending thoracic aortic aneurysm and dissection and control normal aortic segments were from our existing aortic tissue bank as described in our recent publication [ 27 ], respectively.…”

Section: Methodsmentioning

confidence: 99%

MKL1 cooperates with p38MAPK to promote vascular senescence, inflammation, and abdominal aortic aneurysm

Gao

Zhao

et al. 2021

Redox Biology

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Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy. Myocardin related transcription factor A (MRTFA, MKL1) is a multifaceted transcription factor, regulating diverse biological processes. However, a detailed understanding of the mechanistic role of MKL1 in AAA has yet to be elucidated. In this study, we showed induced MKL1 expression in thoracic and abdominal aneurysmal tissues, respectively in both mice and humans. MKL1 global knockout mice displayed reduced AAA formation and aortic rupture compared with wild-type mice. Both gene deletion and pharmacological inhibition of MKL1 markedly protected mice from aortic dissection, an early event in Angiotensin II (Ang II)-induced AAA formation. Loss of MKL1 was accompanied by reduced senescence/proinflammation in the vessel wall and cultured vascular smooth muscle cells (VSMCs). Mechanistically, a deficiency in MKL1 abolished AAA-induced p38 mitogen activated protein kinase (p38MAPK) activity. Similar to MKL1, loss of MAPK14 (p38α), the dominant isoform of p38MAPK family in VSMCs suppressed Ang II-induced AAA formation, vascular inflammation, and senescence marker expression. These results reveal a molecular pathway of AAA formation involving MKL1/p38MAPK stimulation and a VSMC senescent/proinflammatory phenotype. These data support targeting MKL1/p38MAPK pathway as a potential effective treatment for AAA.

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Section: Methodsmentioning

confidence: 99%

MKL1 cooperates with p38MAPK to promote vascular senescence, inflammation, and abdominal aortic aneurysm

Gao

Zhao

et al. 2021

Redox Biology

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“…Written and informed consent was obtained from all patients, and protocols were approved by the local ethics committee ( 46 ). Human AAA material was harvested during surgical repair and stored in complete DMEM/F12 Medium (MilliporeSigma, containing 5% FBS and 1% PBS).…”

Section: Methodsmentioning

confidence: 99%

Lenvatinib halts aortic aneurysm growth by restoring smooth muscle cell contractility

Busch¹,

Pauli²,

Winski³

et al. 2021

JCI Insight

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Rationale: To evaluate the repurposing of lenvatinib, a multi tyrosine kinase inhibitor, in limiting experimental abdominal aortic aneurysm (AAA) growth.Objective: AAA is a disease with high morbidity and mortality, especially in case of rupture. No pharmacologic treatment is currently available. Novel therapeutic strategies are targeting vascular smooth muscle cells (VSMC) and angiogenesis.Repurposing of clinically available drugs has proven its benefit to extend treatment strategies and may be suited to halt aortic dilatation.Findings: Porcine pancreatic elastase (PPE) was used to induce murine AAAs.Systemic and local lenvatinib forms of treatment were evaluated, and RNA profiling identified myosin heavy chain 11 (Myh11) as the most deregulated transcript. Daily oral treatment significantly reduced aneurysm formation in two independent mouse models. In addition, a novel large animal aneurysm model in hypercholesterolemic low-density lipoprotein receptor knockout (LDLR -/-) Yucatan minipigs was applied to endovascularly deliver lenvatinib via drug-eluting balloons (DEB). Here, a single local endovascular delivery blocked AAA progression successfully compared to a DEBdelivered control treatment when reaching 28 days post aneurysm induction.Reduced VSMC proliferation and a restored contractile phenotype were observed in animal tissues (murine and porcine), as well as AAA patient-derived cells. Apart from increasing MYH11 levels, lenvatinib reduced downstream ERK signaling. Conclusion:Lenvatinib is a promising new therapy to limit aortic aneurysm expansion upon local endovascular delivery. The tyrosine kinase inhibitor was able to positively affect pathways of key relevance to human AAA disease. The novel endovascular local delivery using DEBs offers new treatment strategies for additional therapies capable of slowing down aneurysm expansion.

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“…Healthy carotid vessels were obtained from the Forensic Medicine Department. Sample processing for histological analysis was performed by an established procedure 46 , 76 . Briefly, carotid specimens were fixed in formalin and embedded in paraffin (FFPE), cross-sections of 2–3 µm were prepared and stained with H&E and Elastica-van-Gieson (EVG) to evaluate tissue histomorphology and plaque vulnerability.…”

Section: Methodsmentioning

confidence: 99%

Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting

et al. 2020

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Targeting a specific chemokine/receptor axis in atherosclerosis remains challenging. Soluble receptor-based strategies are not established for chemokine receptors due to their discontinuous architecture. Macrophage migration-inhibitory factor (MIF) is an atypical chemokine that promotes atherosclerosis through CXC-motif chemokine receptor-4 (CXCR4). However, CXCR4/CXCL12 interactions also mediate atheroprotection. Here, we show that constrained 31-residue-peptides (‘msR4Ms’) designed to mimic the CXCR4-binding site to MIF, selectively bind MIF with nanomolar affinity and block MIF/CXCR4 without affecting CXCL12/CXCR4. We identify msR4M-L1, which blocks MIF- but not CXCL12-elicited CXCR4 vascular cell activities. Its potency compares well with established MIF inhibitors, whereas msR4M-L1 does not interfere with cardioprotective MIF/CD74 signaling. In vivo-administered msR4M-L1 enriches in atherosclerotic plaques, blocks arterial leukocyte adhesion, and inhibits atherosclerosis and inflammation in hyperlipidemic Apoe−/− mice in vivo. Finally, msR4M-L1 binds to MIF in plaques from human carotid-endarterectomy specimens. Together, we establish an engineered GPCR-ectodomain-based mimicry principle that differentiates between disease-exacerbating and -protective pathways and chemokine-selectively interferes with atherosclerosis.

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Biobanking: Objectives, Requirements, and Future Challenges—Experiences from the Munich Vascular Biobank

Cited by 38 publications

References 53 publications

MKL1 cooperates with p38MAPK to promote vascular senescence, inflammation, and abdominal aortic aneurysm

MKL1 cooperates with p38MAPK to promote vascular senescence, inflammation, and abdominal aortic aneurysm

Lenvatinib halts aortic aneurysm growth by restoring smooth muscle cell contractility

Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting

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