Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematopoietic stem cells (HSCs) can be safely collected from the body, genetically modified, and re-infused into a patient with the goal to express the transgene product for an individual's lifetime. Hematologic defects that can be corrected with an allogeneic bone marrow transplant can theoretically also be treated with gene replacement therapy. Because some genetic disorders affect distinct cell lineages, researchers are utilizing HSC gene transfer techniques using lineage-specific endogenous gene promoters to confine transgene expression to individual cell types (eg, ITGA2B for inherited platelet defects). HSCs appear to be an ideal target for platelet gene therapy because they can differentiate into megakaryocytes which are capable of forming several thousand anucleate platelets that circulate within blood vessels to establish hemostasis by repairing vascular injury. Platelets play an essential role in other biological processes (immune response, angiogenesis) as well as diseased states (atherosclerosis, cancer, thrombosis). Thus, recent advances in genetic manipulation of megakaryocytes could lead to new and improved therapies for treating a variety of disorders. In summary, genetic manipulation of megakaryocytes has progressed to the point where clinically relevant strategies are being developed for human trials for genetic disorders affecting platelets. Nevertheless, challenges still need to be overcome to perfect this field; therefore, strategies to increase the safety and benefit of megakaryocyte gene therapy will be discussed.
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PMID:Megakaryocyte- and megakaryocyte precursor-related gene therapies. 2678 35

The vascular endothelium comprises a continuous single cell layer of endothelial cells which line the entire cardiovascular system. Impaired endothelial function underlies the pathogenesis and contributes to the progression of atherosclerosis. Oxidative stress, vasoconstriction, inflammation, proliferation and thrombosis occur in dysfunctional endothelium while the latter, is primarily mediated by platelet activation and adherence to vascular wall. Despite the primary action of antiplatelet agents including aspirin, P2Y12 ADP receptor antagonists and glycoprotein IIb/IIIa inhibitors, a growing body of literature suggests that an important mechanism of their action involves complex modulation of endothelial function via platelet-endothelial interactions, modification of the inflammatory cytokine cascade and nitric oxide mediated effects. These agents represent the mainstay in pharmacological treatment of all aspects of cardiovascular disease both in primary and secondary prevention. However beyond these properties, it is important to note that pharmacological modification of endothelial dysfunction has been postulated as a therapeutic target for reduction of cardiovascular events.
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PMID:The Impact of Antiplatelet Treatment on Endothelial Function. 2726 35

Background and Purpose- Endovascular treatment for acute intracranial atherosclerosis-related large vessel occlusion (ICAS [+]-LVO) is one of the challenging issues in modern mechanical thrombectomy era. We evaluated procedural and clinical outcomes of endovascular treatment for the ICAS (+)-LVO. We also compared their outcomes with those of large vessel occlusion not associated with intracranial atherosclerosis (ICAS [-]-LVO). Methods- We retrospectively reviewed consecutive patients with acute stroke who underwent endovascular treatment for LVO. Patients were assigned to the ICAS (+)-LVO group or the ICAS (-)-LVO group primarily based on catheter angiogram. Procedural and clinical outcomes were compared between the ICAS (+)-LVO and ICAS (-)-LVO groups. Results- The present study included 318 patients. Fifty-six patients (17.6%) had an ICAS (+)-LVO. Recanalization was achieved in 45 patients in the ICAS (+)-LVO group (80.4%), which was comparable with the ICAS (-)-LVO group (88.5%; P=0.097). However, recanalization using a stent retriever was less successful in the ICAS (+)-LVO (28.9%) than the ICAS (-)-LVO group (93.5%). Of the remaining patients in the ICAS (+)-LVO group, 84.3% of patients required specific rescue treatments appropriate for ICAS, including balloon angioplasty, stenting, and intra-arterial glycoprotein IIb/IIIa inhibitor infusion. The rates of favorable outcomes (46.4% versus 46.9%), death, and symptomatic intracranial hemorrhage were not significantly different between the 2 groups. Glycoprotein IIb/IIIa inhibitor use was not significantly associated with symptomatic intracranial hemorrhage. Conclusions- ICAS (+)-LVO was often refractory to mechanical thrombectomy. With specific rescue treatments appropriate for ICAS, patients in the ICAS (+)-LVO group had a recanalization rate comparable with patients in the ICAS (-)-LVO. With comparable recanalization rate, the clinical outcomes did not differ between patients with ICAS (+)-LVO and ICAS (-)-LVO.
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PMID:Outcomes of Endovascular Treatment for Acute Intracranial Atherosclerosis-Related Large Vessel Occlusion. 3035 4

Background and Purpose: Endovascular treatment (EVT) for acute vertebrobasilar intracranial atherosclerosis-related large vessel occlusion (ICAS-LVO) and its outcomes are not well known. We aimed to evaluate endovascular and clinical outcomes of vertebrobasilar ICAS-LVO patients who underwent EVT. Methods: Consecutive acute stroke patients who underwent EVT for vertebrobasilar LVO were retrospectively reviewed. Patients were assigned to the ICAS (+) or the ICAS (-) group based on angiographical findings. Procedural details and clinical outcomes were compared between the ICAS (+) and ICAS (-) groups. Results: This study included 77 patients with acute vertebrobasilar LVO who underwent EVT. Among the study subjects, 24 (31.2%) had an ICAS-LVO. Recanalization was achieved in 19 patients in the ICAS (+) group (79.2%), which was comparable with the ICAS (-) group (84.9%; p = 0.529). However, recanalization using conventional endovascular modalities (stent retriever thrombectomy, contact aspiration thrombectomy, or intra-arterial urokinase infusion) was less successful in the ICAS (+) group (36.8%) than the ICAS (-) group (100.0%; p < 0.001). All the remaining patients in the ICAS (+) group required specific rescue treatments appropriate for ICAS, including balloon angioplasty, stenting, or intra-arterial glycoprotein IIb/IIIa inhibitor infusion to obtain a successful recanalization. Procedural time was not significantly longer in the ICAS (+) group. The rates of favorable outcomes (37.5% vs. 41.5%; p = 0.740), death, and symptomatic intracerebral hemorrhage were not significantly different between the groups. Conclusion: ICAS-LVO was common in patients who underwent EVT for acute vertebrobasilar LVO. Although conventional modalities were often ineffective for vertebrobasilar ICAS-LVO, a comparable recanalization rate could be obtained with ICAS-specific modalities. Recanalization rate and procedural time were comparable, and clinical outcomes did not differ between patients with or without ICAS-LVO.
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PMID:Endovascular and Clinical Outcomes of Vertebrobasilar Intracranial Atherosclerosis-Related Large Vessel Occlusion. 3094 Oct 84

Background and Purpose- Intracranial atherosclerosis (ICAS) is an important cause of large vessel occlusion and poses unique challenges for emergent endovascular thrombectomy. The risk factor profile and therapeutic outcomes of patients with ICAS-related occlusions (ICAS-O) are unclear. We performed a systematic review and meta-analysis of studies reporting the clinical features and thrombectomy outcomes of large vessel occlusion stroke secondary to underlying ICAS (ICAS-O) versus those of other causes (non-ICAS-O). Methods- A literature search on thrombectomy for ICAS-O was performed. Random-effect meta-analysis was used to analyze the prevalence of stroke risk factors and outcomes of thrombectomy between ICAS-O and non-ICAS-O groups. Results- A total of 1967 patients (496 ICAS-O and 1471 non-ICAS-O) were included. The ICAS-O group had significantly higher prevalence of hypertension (odds ratio [OR] 1.46; 95% CI, 1.10-1.93), diabetes mellitus (OR, 1.68; 95% CI, 1.29-2.20), dyslipidemia (OR, 1.94; 95% CI, 1.04-3.62), smoking history (OR, 2.11; 95% CI, 1.40-3.17) but less atrial fibrillation (OR, 0.20; 95% CI, 0.13-0.31) than the non-ICAS-O group. About thrombectomy outcomes, ICAS-O had higher intraprocedural reocclusion rate (OR, 23.7; 95% CI, 6.96-80.7), need for rescue balloon angioplasty (OR, 9.49; 95% CI, 4.11-21.9), rescue intracranial stenting (OR, 14.9; 95% CI, 7.64-29.2), and longer puncture-to-reperfusion time (80.8 versus 55.5 minutes, mean difference 21.3; 95% CI, 11.3-31.3). There was no statistical difference in the rate of final recanalization (modified Thrombolysis in Cerebral Infarction score of 2b/3; OR, 0.67; 95% CI, 0.36-1.27), symptomatic intracerebral hemorrhage (OR, 0.79; 95% CI, 0.50-1.24), good functional outcome (modified Rankin Scale score of 0-2; OR, 1.16; 95% CI, 0.85-1.58), and mortality (OR, 0.94; 95% CI, 0.64-1.39) between ICAS-O and non-ICAS-O. Conclusions- Patients with ICAS-O display a unique risk factor profile and technical challenges for endovascular reperfusion therapy. Intraprocedural reocclusion occurs in one-third of patients with ICAS-O. Intraarterial glycoprotein IIb/IIIa inhibitors infusion, balloon angioplasty, and intracranial stenting may be viable rescue treatment to achieve revascularization, resulting in comparable outcomes to non-ICAS-O.
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PMID:Thrombectomy Outcomes of Intracranial Atherosclerosis-Related Occlusions. 3108 27


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