Abstract: The present invention relates to a preparation method for a self-organized cardiac organoid. The invention also relates to a cardiac tissue organoid obtained by the method and to its use in regenerative medicine, as a tissue implant, or in drug screening.

Abstract: The present invention relates to a combination of inhibitory nucleic acid agents directed at a combination of miRNAs for treatment of heart failure. The combination of inhibited miRNAs comprises one of the groups selected from miR-1a, and miR-15b, or miR-1a, miR-15b and miR-27b, or miR-1a, miR-27b and miR-34a. The combinatorial inhibition of these miRNAs is shown to increase cardiomyocyte proliferation.

Abstract: The invention relates to a method for generating a cardiac tissue mimetic, comprising the steps of mixing cardiomyocytes (CM) and fibroblasts (FB) at a ratio from 2.5:1 to 10:1, thereby providing a first mixture, incubating said first mixture, such that said cardiomyocytes and said fibroblasts form a spherical structure, adding endothelial cells (EC) to said spherical structure at a ratio of cardiomyocytes (CM) to endothelial cells (EC) from 1.5:1 to 4:1, thereby providing a second mixture, and incubating said second mixture, such that a cardiac tissue mimetic is formed. The invention further relates to a cardiac tissue mimetic comprising cardiomyocytes (CM), endothelial cells (EC), and fibroblasts (FB), wherein said cardiac tissue mimetic comprises sarcomeric structures and vascular structures. Further aspects of the invention are the cardiac tissue mimetic for use in a method for heart tissue repair or replacement and a method for screening a compound using a cardiac tissue mimetic.

Abstract: The present invention provides novel non-coding RNAs (lncRNA) that were identified to be expressed in pericytes upon hypoxia. The lncRNA of the invention positively affect Platelet-derived Growth Factor Receptor (PDGFR) beta expression, pericytes proliferation and pericyte recruitment to endothelial cells. The invention provides inhibitors of the lncRNA for use in the treatment of diseases mediated by PDGFR expression. For example the invention described antisense approaches to target the lncRNA of the invention. Furthermore, the invention provides lncRNA inhibitors as amplifier of therapeutic PDGFR inhibitors such as imatinib or other tyrosine kinase inhibitors. lncRNA inhibitors and methods for screening modulators of lncRNA expression and/or function are provided.

Abstract: The present invention associates multiple circular (circRNA) with key functions of endothelial cells. The present invention provides circRNA transcripts that are correlated with cardiovascular diseases, in particular acute myocardial infarction. The circRNA of the invention therefore serve as biomarkers in the diagnosis of cardiovascular disorders. The invention provides the new nucleic acid molecules as well as diagnostic kits and compositions comprising the nucleic acids. Modulation of the expression of the circRNA of the invention further leads to endothelial cell sprouting, and therefore is applied as a treatment for cardiovascular diseases or pathological angiogenesis. The invention provides therapeutic agents modulating circRNA expression or function. Further aspects of the invention provide novel circRNA for the treatment of inflammatory diseases.

Abstract: The present invention associates multiplelong non-coding RNA (lncRNA) with key functions of endothelial cells. The lncRNA of the present invention are therefore useful as novel drug targets for the manufacturing of medicines for the treatment of cardiovascular diseases or pathological angiogenesis in context of proliferative diseases such as cancer. Modulation of the function or expression of the lncRNA of invention can induce or repress angiogenesis and vessel growth or repair in endothelial cells. Provided are further methods for the modulation of endothelial cell functions in vitro, for example, in the context of tissue engineering.

Abstract: The invention relates to a method for influencing the miR-92 expression in a cell, comprising the following steps: (a) providing a cell; and (b1) reducing the miR-92 expression in the cell in order to promote the vascularization or vessel repair by introducing an antisense molecule against miR-92 into the cell, or (b2) increasing the miR-92 expression in the cell for an inhibition of the tumor angiogenesis by introducing a construct into the cell, wherein said construct includes an expressible miR-92 sequence. Furthermore, the invention relates to a pharmaceutical composition, comprising an agent for reducing the miR-92 activity or expression in a cell in the form of an antisense molecule against miR-92, or an agent for increasing the miR-92 expression in a cell in the form of a construct for expressing miR-92.

Abstract: The invention relates to a method for influencing the miR-92 expression in a cell, comprising the following steps: (a) providing a cell; and (b1) reducing the miR-92 expression in the cell in order to promote the vascularization or vessel repair by introducing an antisense molecule against miR-92 into the cell, or (b2) increasing the miR-92 expression in the cell for an inhibition of the tumor angiogenesis by introducing a construct into the cell, wherein said construct includes an expressible miR-92 sequence. Furthermore, the invention relates to a pharmaceutical composition, comprising an agent for reducing the miR-92 activity or expression in a cell in the form of an antisense molecule against miR-92, or an agent for increasing the miR-92 expression in a cell in the form of a construct for expressing miR-92.

Abstract: The invention relates to a method for influencing the miR-92 expression in a cell, comprising the following steps: (a) providing a cell; and (b1) reducing the miR-92 expression in the cell in order to promote the vascularization or vessel repair by introducing an antisense molecule against miR-92 into the cell, or (b2) increasing the miR-92 expression in the cell for an inhibition of the tumor angiogenesis by introducing a construct into the cell, wherein said construct includes an expressible miR-92 sequence. Furthermore, the invention relates to a pharmaceutical composition, comprising an agent for reducing the miR-92 activity or expression in a cell in the form of an antisense molecule against miR-92, or an agent for increasing the miR-92 expression in a cell in the form of a construct for expressing miR-92.

Abstract: The present invention relates to antagonists of the expression and/or the function of the micro RNA miRNA-29 for use in the prevention and/or treatment of aortic aneurysms. Further disclosed is a method for the identification of miRNA-29 antagonists, a pharmaceutical composition comprising said miRNA-29 antagonists and a method for preventing and treating age-related aortic aneurysm formation in a subject in need of such a treatment.

Abstract: Improving cell therapy and tissue regeneration in a patient suffering from a cardiovascular or a neurological disease by treating a tissue of the patient with shock waves and/or applying to the patient a therapeutically effective amount of stem cells and/or progenitor cells. Such treatment increases expression of chemoattractants, pro-angiogenic factors, and pro-survival factors. The chemoattractants can be, for example, vascular endothelial growth factor (VEGF) or stromal cell derived factor 1 (SDF-1). For example, the treated tissue can be located in the patient's heart or in a skeletal muscle of the patient, and the shock waves can be extracorporeal shock waves (ESW) or intracorporeal shock waves. The cardiovascular disease can have an ischemic or non-ischemic etiology. For example, the cardiovascular disease can be a myocardial infarction, ischemic cardiomyopathy, or a dilatative cardiomyopathy. For example, the neurological disease can be a peripheral neuropathy or neuropathic pain.

Abstract: The invention relates to a method for influencing the miR-92 expression in a cell, comprising the following steps: (a) providing a cell; and (b1) reducing the miR-92 expression in the cell in order to promote the vascularization or vessel repair by introducing an antisense molecule against miR-92 into the cell, or (b2) increasing the miR-92 expression in the cell for an inhibition of the tumor angiogenesis by introducing a construct into the cell, wherein said construct includes an expressible miR-92 sequence. Furthermore, the invention relates to a pharmaceutical composition, comprising an agent for reducing the miR-92 activity or expression in a cell in the form of an antisense molecule against miR-92, or an agent for increasing the miR-92 expression in a cell in the form of a construct for expressing miR-92.

Abstract: The invention relates to a method for influencing the miR-92 expression in a cell, comprising the following steps: (a) providing a cell; and (b1) reducing the miR-92 expression in the cell in order to promote the vascularization or vessel repair by introducing an antisense molecule against miR-92 into the cell, or (b2) increasing the miR-92 expression in the cell for an inhibition of the tumor angiogenesis by introducing a construct into the cell, wherein said construct includes an expressible miR-92 sequence. Furthermore, the invention relates to a pharmaceutical composition, comprising an agent for reducing the miR-92 activity or expression in a cell in the form of an antisense molecule against miR-92, or an agent for increasing the miR-92 expression in a cell in the form of a construct for expressing miR-92.

Abstract: The present invention relates to treating or preventing age-related cardiomyopathy by modulating the expression or activity of a miR-34 family member and/or PNUTS. Methods of treating or preventing age-related cardiomyopathy include administering an inhibitor of miR-34 expression or activity or an agonist of PNUTS expression or activity. Also provided herein are methods of treating or preventing cardiac fibrosis and myocardial infarction by administering an inhibitor of miR-34 expression or activity or an agonist of PNUTS expression or activity.

Abstract: The invention relates to novel markers of vascular inflammation and combinations thereof as diagnostic and prognostic tools in patients with cardiovascular diseases. The markers also act as tools that facilitate the selection of active ingredients for the treatment of such diseases, and finally act as starting points for the treatment of cardiovascular diseases. Furthermore, the invention relates to the creation of an individual risk profile of negative events that are associated with the progression of arteriosclerosis.

Abstract: The present invention relates to antagonists of the expression and/or the function of the micro RNA miRNA-29 for use in the prevention and/or treatment of aortic aneurysms. Further disclosed is a method for the identification of miRNA-29 antagonists, a pharmaceutical composition comprising said miRNA-29 antagonists and a method for preventing and treating age-related aortic aneurysm formation in a subject in need of such a treatment.

Abstract: The invention relates to novel markers of vascular inflammation and combinations thereof as diagnostic and prognostic tools in patients with cardiovascular diseases. The markers also act as tools that facilitate the selection of active ingredients for the treatment of such diseases, and finally act as starting points for the treatment of cardiovascular diseases. Furthermore, the invention relates to the creation of an individual risk profile of negative events that are associated with the progression of arteriosclerosis.

Abstract: The invention relates to novel markers of vascular inflammation and combinations thereof as diagnostic and prognostic tools in patients with cardiovascular diseases. The markers also act as tools that facilitate the selection of active ingredients for the treatment of such diseases, and finally act as starting points for the treatment of cardiovascular diseases. Furthermore, the invention relates to the creation of an individual risk profile of negative events that are associated with the progression of arteriosclerosis.

Abstract: The invention relates to a method for influencing the miR-92 expression in a cell, comprising the following steps: (a) providing a cell; and (b1) reducing the miR-92 expression in the cell in order to promote the vascularization or vessel repair by introducing an antisense molecule against miR-92 into the cell, or (b2) increasing the miR-92 expression in the cell for an inhibition of the tumor angiogenesis by introducing a construct into the cell, wherein said construct includes an expressible miR-92 sequence. Furthermore, the invention relates to a pharmaceutical composition, comprising an agent for reducing the miR-92 activity or expression in a cell in the form of an antisense molecule against miR-92, or an agent for increasing the miR-92 expression in a cell in the form of a construct for expressing miR-92.

Abstract: The present invention relates to the use of compounds which enhance the transcription of endothelial nitric oxide synthase (eNOS) for treating stem and progenitor cells in the cell therapy of patients with ischemic heart diseases such as coronary heart disease or ischemic cardiomyopathy. Treatment of such cells which are isolated from bone marrow, for example, with an eNOS transcription enhancer prior to their administration improves their functional activity and ameliorates neovascularization of the heart and cardiac regeneration.