Plaque erosion,together with plaque rupture,is a common cause for acute coronary syndrome(ACS).Plaque erosion alone is responsible for about one third of the patients with ACS.Eroded plaque is defined as thrombosed,en...Plaque erosion,together with plaque rupture,is a common cause for acute coronary syndrome(ACS).Plaque erosion alone is responsible for about one third of the patients with ACS.Eroded plaque is defined as thrombosed,endothelium-absent and non-ruptured but often-inflamed plaques based on histological findings.Even though there is efficient imaging technologies to detect the eroded plaque in vivo and tailored treatment strategy has also been developed for ACScaused by erosion in clinics,the pathogenesis mechanisms that cause plaque erosion are not fully understood.It is widely postulated that thrombus formation and endothelial apoptosis(the precursors of plaque erosion)have closed association with biomechanical conditions in the coronary vessel.Revealing of the mechanical conditions in the eroded plaque could advance our knowledge in understanding the formation of plaque erosion.To this end,patient-specific OCT-based fluid-structure interaction(FSI)models were developed to investigate the plaque biomechanical conditions and investigate the impact of erosioninduced inflammation on biomechanical conditions.In vivo OCTand Biplane X-ray angiographic data of eroded coronary plaque were acquired from one male patient(age:64). OCT images were segmented manually with external elastic membrane contour and the trailing edge of the lipid-rich necrotic core(lipid)assumed to have positive remodeling ratio 1.1.Locations with luminal surface having direct contact with intraluminal thrombus on OCT images were identified erosion sites.Fusion of OCT and biplane X-ray angiographic data were performed to obtain the 3D coronary geometry.OCT-based FSI models with pre-shrink-stretch process and anisotropic material properties were constructed following previously established procedures.To reflect tissue weakening caused by erosion-induced inflammation,the material stiffness of plaque intima at the erosion site was adjust to one tenth of un-eroded fibrous plaque tissue.Three FSI models were constructed to investigate the impacts of inflammation and lipid component on plaque biomechanics:M1,without erosion(this means plaque intima at the erosion sites were not softened)and without inclusion of lipid component;M2,with erosion but no lipid;M3,with erosion and inclusion of lipid.FSI models were solved by ADINA to obtain the biomechanical conditions at peak blood pressure including plaque wall stress/strain(PWS/PWSn)and flow wall shear stress(WSS).The average values of three biomechanical conditions at the erosion sites and at the fibrous cap overlaying lipid component were calculated from three models for analysis.The results of M1 and M2 were compared to investigate the impact of erosion-induced inflammation on plaque biomechanics.Mean PWS value decreases from 49.98 kPa to 18.83 kPa(62.32%decrease)while Mean PWSn value increases from 0.123 1 to 0.138 4(12%increase)as the material stiffness becomes 10times soft.Comparing M2 and M3 at the cap sites,M3(with inclusion of lipid)will elevates mean PWS and PWSn values by48.59%and 16.09%,respectively.The impacts of erosion and lipid on flow shear stress were limited(<2%).To conclude,erosion-induced inflammation would lead to lower stress distribution but larger strain distribution,while lipid would elevate both stress and strain conditions.This shows the influence of erosion and lipid component has impacts on stress/strain cal-culations which are closely related to plaque assessment.展开更多
Acute coronary syndrome(ACS)is the main cause of death worldwide and the leading cause of disease burden in high-income countries.ACS refers to a constellation of clinical symptoms that are compatible with acute myoca...Acute coronary syndrome(ACS)is the main cause of death worldwide and the leading cause of disease burden in high-income countries.ACS refers to a constellation of clinical symptoms that are compatible with acute myocardial ischemia.It describes a spectrum of clinical manifestations that result from a common pathophysiological process.The most common cause of ACS are rupture of an atherosclerotic lesion containing a large necrotic core and a thin fibrous cap followed by acute luminal thrombosis.It was thought that a high-resolution imaging modality would be ideal to detect high-risk plaques before their disruption and the formation of an occlusive thrombus.Optical coherence tomography has proven to be an invaluable tool in early detection of high-risk plaques and particularly in the understanding of ACS.This review focuses on the current evidence for the role of optical coherence tomography in the diagnosis and treatment of patients with ACS.展开更多
Secretoneurin （SN） is a neuropeptide derived from specific proteolytic processing of the precursor secretogranin II （Sgll）. In zebrafish and other teleosts, there are two paralogs named sglla and sgllb. Our result...Secretoneurin （SN） is a neuropeptide derived from specific proteolytic processing of the precursor secretogranin II （Sgll）. In zebrafish and other teleosts, there are two paralogs named sglla and sgllb. Our results showed that neurons expressing sgllb were aligned with central arteries in the hindbrain, demonstrating a close neurovascular association. Both sgllb-/- and sgllo-/-/sgllb-/- mutant embryos were defective in hindbrain central artery development due to impairment of migration and proliferation of central artery cells. Further study revealed that sgllb is non-ceU autonomous and required for central artery development. Hindbrain arterial and venous network identities were not affected in sgllb-/- mutant embryos, and the mRNA levels of Notch and VEGF pathway-related genes were not altered. However, the activation of MAPK and PI3K/AKT pathways was inhibited in sgllb-/- mutant embryos. Reactivation of MAPK or PI3K/AKT in endothelial cells could partially rescue the central artery developmental defects in the sgllb mutants. This studV provides the first in vivo evidence that sgllb ptavs a critical rote in neurovascutar modeling of the hindbrain. Targeting the Sgll system may, therefore, represent a new avenue for the treatment of vascular defects in the central nervous system.展开更多
基金supported in part by NSFC ( 11672001,11802060)Jiangsu NSF ( BK20180352)Jiangsu Province Science and Technology Agency ( BE2016785)
文摘Plaque erosion,together with plaque rupture,is a common cause for acute coronary syndrome(ACS).Plaque erosion alone is responsible for about one third of the patients with ACS.Eroded plaque is defined as thrombosed,endothelium-absent and non-ruptured but often-inflamed plaques based on histological findings.Even though there is efficient imaging technologies to detect the eroded plaque in vivo and tailored treatment strategy has also been developed for ACScaused by erosion in clinics,the pathogenesis mechanisms that cause plaque erosion are not fully understood.It is widely postulated that thrombus formation and endothelial apoptosis(the precursors of plaque erosion)have closed association with biomechanical conditions in the coronary vessel.Revealing of the mechanical conditions in the eroded plaque could advance our knowledge in understanding the formation of plaque erosion.To this end,patient-specific OCT-based fluid-structure interaction(FSI)models were developed to investigate the plaque biomechanical conditions and investigate the impact of erosioninduced inflammation on biomechanical conditions.In vivo OCTand Biplane X-ray angiographic data of eroded coronary plaque were acquired from one male patient(age:64). OCT images were segmented manually with external elastic membrane contour and the trailing edge of the lipid-rich necrotic core(lipid)assumed to have positive remodeling ratio 1.1.Locations with luminal surface having direct contact with intraluminal thrombus on OCT images were identified erosion sites.Fusion of OCT and biplane X-ray angiographic data were performed to obtain the 3D coronary geometry.OCT-based FSI models with pre-shrink-stretch process and anisotropic material properties were constructed following previously established procedures.To reflect tissue weakening caused by erosion-induced inflammation,the material stiffness of plaque intima at the erosion site was adjust to one tenth of un-eroded fibrous plaque tissue.Three FSI models were constructed to investigate the impacts of inflammation and lipid component on plaque biomechanics:M1,without erosion(this means plaque intima at the erosion sites were not softened)and without inclusion of lipid component;M2,with erosion but no lipid;M3,with erosion and inclusion of lipid.FSI models were solved by ADINA to obtain the biomechanical conditions at peak blood pressure including plaque wall stress/strain(PWS/PWSn)and flow wall shear stress(WSS).The average values of three biomechanical conditions at the erosion sites and at the fibrous cap overlaying lipid component were calculated from three models for analysis.The results of M1 and M2 were compared to investigate the impact of erosion-induced inflammation on plaque biomechanics.Mean PWS value decreases from 49.98 kPa to 18.83 kPa(62.32%decrease)while Mean PWSn value increases from 0.123 1 to 0.138 4(12%increase)as the material stiffness becomes 10times soft.Comparing M2 and M3 at the cap sites,M3(with inclusion of lipid)will elevates mean PWS and PWSn values by48.59%and 16.09%,respectively.The impacts of erosion and lipid on flow shear stress were limited(<2%).To conclude,erosion-induced inflammation would lead to lower stress distribution but larger strain distribution,while lipid would elevate both stress and strain conditions.This shows the influence of erosion and lipid component has impacts on stress/strain cal-culations which are closely related to plaque assessment.
文摘Acute coronary syndrome(ACS)is the main cause of death worldwide and the leading cause of disease burden in high-income countries.ACS refers to a constellation of clinical symptoms that are compatible with acute myocardial ischemia.It describes a spectrum of clinical manifestations that result from a common pathophysiological process.The most common cause of ACS are rupture of an atherosclerotic lesion containing a large necrotic core and a thin fibrous cap followed by acute luminal thrombosis.It was thought that a high-resolution imaging modality would be ideal to detect high-risk plaques before their disruption and the formation of an occlusive thrombus.Optical coherence tomography has proven to be an invaluable tool in early detection of high-risk plaques and particularly in the understanding of ACS.This review focuses on the current evidence for the role of optical coherence tomography in the diagnosis and treatment of patients with ACS.
文摘Secretoneurin （SN） is a neuropeptide derived from specific proteolytic processing of the precursor secretogranin II （Sgll）. In zebrafish and other teleosts, there are two paralogs named sglla and sgllb. Our results showed that neurons expressing sgllb were aligned with central arteries in the hindbrain, demonstrating a close neurovascular association. Both sgllb-/- and sgllo-/-/sgllb-/- mutant embryos were defective in hindbrain central artery development due to impairment of migration and proliferation of central artery cells. Further study revealed that sgllb is non-ceU autonomous and required for central artery development. Hindbrain arterial and venous network identities were not affected in sgllb-/- mutant embryos, and the mRNA levels of Notch and VEGF pathway-related genes were not altered. However, the activation of MAPK and PI3K/AKT pathways was inhibited in sgllb-/- mutant embryos. Reactivation of MAPK or PI3K/AKT in endothelial cells could partially rescue the central artery developmental defects in the sgllb mutants. This studV provides the first in vivo evidence that sgllb ptavs a critical rote in neurovascutar modeling of the hindbrain. Targeting the Sgll system may, therefore, represent a new avenue for the treatment of vascular defects in the central nervous system.
