Molecular Biology and Human Genetics

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Browsing Molecular Biology and Human Genetics by Subject "Abdominal aneurysm"

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    Association of simple renal cysts and chronic kidney disease with large abdominal aortic aneurysm
    (BMC (part of Springer Nature), 2020-05-29) Miszczuk, Milena; Müller, Verena; Althoff, Christian E.; Stroux, Andrea; Widhalm, Daniela; Dobberstein, Andy; Greiner, Andreas; Kuivaniemi, Helena; Hinterseher, Irene
    Background: Abdominal aortic aneurysms (AAA) primarily affect men over 65 years old who often have many other diseases, with similar risk factors and pathobiological mechanisms to AAA. The aim of this study was to assess the prevalence of simple renal cysts (SRC), chronic kidney disease (CKD), and other kidney diseases (e.g. nephrolithiasis) among patients presenting with AAA. Methods: Two groups of patients (97 AAA and 100 controls), with and without AAA, from the Surgical Clinic Charité, Berlin, Germany, were selected for the study. The control group consisted of patients who were evaluated for a kidney donation (n = 14) and patients who were evaluated for an early detection of a melanoma recurrence (n = 86). The AAA and control groups were matched for age and sex. Medical records were analyzed and computed tomography scans were reviewed for the presence of SRC and nephrolithiasis. Results: SRC (74% vs. 57%; p<0.016) and CKD (30% vs. 8%; p<0.001) were both more common among AAA than control group patients. On multivariate analysis, CKD, but not SRC, showed a strong association with AAA. Conclusions: Knowledge about pathobiological mechanisms and association between CKD and AAA could provide better diagnostic and therapeutic approaches for these patients.
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    Pharmacological inhibition of Notch signaling regresses pre-established abdominal aortic aneurysm
    (Nature Research, 2019-09-17) Sharma, Neekun; Dev, Rishabh; Ruiz-Rosado, Juan de Dios; Partida-Sanchez, Santiago; Guerau-de-Arellano, Mireia; Dhakal, Pramod; Kuivaniemi, Helena; Hans, Chetan P.
    ENGLISH ABSTRACT: Abdominal aortic aneurysm (AAA) is characterized by transmural infiltration of myeloid cells at the vascular injury site. Previously, we reported preventive effects of Notch deficiency on the development of AAA by reduction of infiltrating myeloid cells. In this study, we examined if Notch inhibition attenuates the progression of pre-established AAA and potential implications. Pharmacological Notch inhibitor (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-(S)-phenylglycine t-butyl ester; DAPT) was administered subcutaneously three times a week starting at day 28 of angiotensin II (AngII) infusion. Progressive increase in pulse wave velocity (PWV), maximal intra-luminal diameter (MILD) and maximal external aortic diameter (MEAD) were observed at day 56 of the AngII. DAPT prevented such increase in MILD, PWV and MEAD (P < 0.01). Histologically, the aortae of DAPT-treated Apoe−/− mice had significant reduction in inflammatory response and elastin fragmentation. Naked collagen microfibrils and weaker banded structure observed in the aortae of Apoe−/− mice in response to AngII, were substantially diminished by DAPT. A significant decrease in the proteolytic activity in the aneurysmal tissues and vascular smooth muscle cells (vSMCs) was observed with DAPT (P < 0.01). In human and mouse AAA tissues, increased immunoreactivity of activated Notch signaling correlated strongly with CD38 expression (R2 = 0.61). Collectively, we propose inhibition of Notch signaling as a potential therapeutic target for AAA progression.