Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in D374Y-PCSK9 Hypercholesterolemic Minipigs
| Autor: | Niels Peter Andersen, Anouk L. Post, Jacob F. Bentzon, Martin M. Bjørklund, Ranil de Silva, Alessio Mattesini, Carlo Di Mario, Anna K. Grøndal, Rob Krams, Ryan M. Pedrigi, Vikram V. Mehta, Nilesh Pareek, Niels Ramsing Holm, Hans Erik Bøtker, Gianni Dall'Ara, Nicolas Foin, Christian Bo Poulsen, Erling Falk, Enrico Petretto, Justin E. Davies, Winston Banya, Ismail Dogu Kilic |
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| Přispěvatelé: | Other Research, Biomedical Engineering and Physics, Graduate School, Poulsen, Christian Bo, Mehta, Vikram V., Holm, Niels Ramsing, Pareek, Nilesh, Post, Anouk L., Kilic, Ismail Dogu, Banya, Winston A.S., Dall'Ara, Gianni, Mattesini, Alessio, Bjørklund, Martin M., Andersen, Niels P., Grøndal, Anna K., Petretto, Enrico, Foin, Nicola, Davies, Justin E., Di Mario, Carlo, Bentzon, Jacob Fog, Bøtker, Hans Erik, Falk, Erling, Krams, Rob, De Silva, Ranil, Royal Brompton & Harefield NHS Foundation Trust, British Heart Foundation |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cardiac & Cardiovascular Systems
Time Factors Swine medicine.medical_treatment Hemodynamics PROGRESSION hemodynamics Coronary Angiography Animals Genetically Modified biophysics Intravascular ultrasound Stent 1102 Cardiorespiratory Medicine and Haematology Tomography IN-VIVO Coronary Vessel Atherosclerotic Plaque medicine.diagnostic_test Optical coherence atherogenesis REGIONS Coronary Vessels Plaque Atherosclerotic Shear stre SCAFFOLD IMPLANTATION medicine.anatomical_structure Atherosclerosi Cardiology Swine Miniature Stents Proprotein Convertases Shear Strength Cardiology and Cardiovascular Medicine Life Sciences & Biomedicine Tomography Optical Coherence medicine.medical_specialty thin cap fibroatheroma Time Factor CORONARY ATHEROSCLEROTIC PLAQUE Hypercholesterolemia shear stress 1117 Public Health and Health Services Coronary circulation Internal medicine Coronary Circulation Physiology (medical) INTRAVASCULAR ULTRASOUND Shear stress medicine Animals Endothelium Hemodynamic optical coherence tomography Science & Technology business.industry Animal 1103 Clinical Sciences NATURAL-HISTORY Blood flow Atherosclerosis medicine.disease ENDOTHELIAL SHEAR-STRESS Proprotein Convertase Surgery Stenosis Disease Models Animal Thin-cap fibroatheroma Peripheral Vascular Disease Cardiovascular System & Hematology Biophysic Regional Blood Flow Cardiovascular System & Cardiology PATTERNS UPDATE Stress Mechanical business |
| Zdroj: | Circulation, 132(11), 1003-1012. Lippincott Williams and Wilkins Pedrigi, R M, Poulsen, C B, Mehta, V V, Holm, N R, Pareek, N, Post, A L, Kilic, I D, Banya, W A S, Dall'Ara, G, Mattesini, A, Bjørklund, M M, Andersen, N P, Grøndal, A K, Petretto, E, Foin, N, Davies, J E, Di Mario, C, Bentzon, J F, Bøtker, H E, Falk, E, Krams, R & de Silva, R 2015, ' Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in D374Y-PCSK9 Hypercholesterolemic Minipigs ', Circulation Research . https://doi.org/10.1161/CIRCULATIONAHA.115.016270 |
| ISSN: | 0009-7322 |
| DOI: | 10.1161/CIRCULATIONAHA.115.016270 |
| Popis: | Background— Although disturbed flow is thought to play a central role in the development of advanced coronary atherosclerotic plaques, no causal relationship has been established. We evaluated whether inducing disturbed flow would cause the development of advanced coronary plaques, including thin cap fibroatheroma. Methods and Results— D374Y -PCSK9 hypercholesterolemic minipigs (n=5) were instrumented with an intracoronary shear-modifying stent (SMS). Frequency-domain optical coherence tomography was obtained at baseline, immediately poststent, 19 weeks, and 34 weeks, and used to compute shear stress metrics of disturbed flow. At 34 weeks, plaque type was assessed within serially collected histological sections and coregistered to the distribution of each shear metric. The SMS caused a flow-limiting stenosis, and blood flow exiting the SMS caused regions of increased shear stress on the outer curvature and large regions of low and multidirectional shear stress on the inner curvature of the vessel. As a result, plaque burden was ≈3-fold higher downstream of the SMS than both upstream of the SMS and in the control artery ( P P P P Conclusions— These data support a causal role for lowered and multidirectional shear stress in the initiation of advanced coronary atherosclerotic plaques. Persistently lowered shear stress appears to be the principal flow disturbance needed for the formation of thin cap fibroatheroma. |
| Databáze: | OpenAIRE |
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