Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Ex Input:
Context: To test the hypothesis that pharmacological plasminogen activator inhibitor (PAI)-1 inhibition protects against renin-angiotensin-aldosterone system-induced cardiovascular injury, the effect of a novel orally active small-molecule PAI-1 inhibitor, PAI-039, was examined in a mouse model of angiotensin (Ang) II-induced vascular remodeling and cardiac fibrosis.', 'Uninephrectomized male C57BL/6J mice were randomized to vehicle subcutaneus, Ang II (1 mug/h) subcutaneous, vehicle+PAI-039 (1 mg/g chow), or Ang II+PAI-039 during high-salt intake for 8 weeks. Ang II caused significant medial, adventitial, and aortic wall thickening compared with vehicle. PAI-039 attenuated Ang II-induced aortic remodeling without altering the pressor response to Ang II. Ang II increased heart/body weight ratio and cardiac fibrosis. PAI-039 did not attenuate the effect of Ang II on cardiac hypertrophy and increased fibrosis. The effect of PAI-039 on Ang II/salt-induced aortic remodeling and cardiac fibrosis was comparable to the effect of genetic PAI-1 deficiency. Ang II increased aortic mRNA expression of PAI-1, collagen I, collagen III, fibronectin, osteopontin, monocyte chemoattractant protein-1, and F4/80; PAI-039 significantly decreased the Ang II-induced increase in aortic osteopontin expression at 8 weeks.
Answer: This study demonstrates that pharmacological inhibition of PAI-1 protects against Ang II-induced aortic remodeling. Future studies are needed to determine whether the interactive effect of Ang II/salt and reduced PAI-1 activity on cardiac fibrosis is species-specific. In this study, the effect of pharmacological PAI-1 inhibition in a mouse model of Ang II-induced vascular remodeling and cardiac fibrosis was examined. PAI-1 inhibition significantly attenuated Ang II-induced aortic medial and wall thickening, but not cardiac hypertrophy, and enhanced Ang II/salt-induced cardiac fibrosis.

Ex Output:
Does pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 attenuate angiotensin II/salt-induced aortic remodeling?


Ex Input:
Context: To simultaneously study the effect of a selective cyclooxygenase-2 (COX-2) inhibitor and that of a classic non-steroidal anti-inflammatory drug (NSAID) on the expression of pro-inflammatory genes in the cartilage of patients with severe knee osteoarthritis (OA) and in cultured human OA chondrocytes.', 'A 3-month clinical trial was carried out on 30 patients with severe knee OA scheduled for knee replacement surgery. Patients were randomized into two groups: patients treated with celecoxib (CBX) and patients treated with aceclofenac (ACF). OA patients who did not want to be treated served as the control group. After surgery, cartilage was processed for molecular biology studies. We also employed cultured chondrocytes from different OA patients to examine NSAID effects on pro-inflammatory gene expression in cells stimulated with interleukin (IL)-1beta.', 'Both CBX and ACF inhibited COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and inducible nitric oxide synthase (iNOS) synthesis in the articular cartilage of OA patients. In cultured chondrocytes, both NSAID decreased COX-2 and mPGES-1 synthesis and prostaglandin E2 (PGE2) release induced by IL-1beta, while no effect was observed on nitric oxide or iNOS synthesis. In OA patients, only CBX decreased tumor necrosis factor alpha and IL-1beta expression in the cartilage, while both NSAID diminished IL-1beta induced cytokine synthesis in cultured OA chondrocytes.
Answer: Both NSAID diminished PGE2 release and induced a decrease in COX-2 and mPGES-1 synthesis in the cartilage from OA patients and in OA chondrocytes. These data suggest that prolonged therapy with PGE2 blocking agents decreases PGE2 production not only by direct inhibition of COX-2 activity, but also by down-regulating COX-2 and mPGES-1 synthesis in the cartilage. However, CBX and ACF seem to have a different anti-inflammatory profile in controlling pro-inflammatory gene expression in the cartilage.

Ex Output:
Does long-term NSAID treatment directly decrease COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis?


Ex Input:
Context: Cerebrovascular accidents (CVAs) frequently coexist with coronary artery disease (CAD) and adversely affect prognosis in patients with CAD; however, fewer studies have investigated the role of prior ischemic stroke on the outcomes of percutaneous coronary intervention (PCI). The aim of this study was to determine the safety and effectiveness of PCI in patients with a prior ischemic stroke.', 'A review of patients who underwent PCI between June 2003 and September 2005 (n=3893) at the Beijing Anzhen Hospital of Capital University of Medical Science, identified 295 PCI patients with a prior ischemic stroke (≥ 3 months) and 3598 patients without a prior stroke. To investigate whether prior history of an ischemic stroke was independently associated with increased risk of adverse PCI outcomes, prognostic parameters were analyzed using univariate analysis and Cox multivariate regression analysis. Propensity score analysis was then used to match the two subgroups of patients based on multiple factors known to impact cardiac outcome.', 'Patients with a prior ischemic stroke had more frequent high-risk baseline characteristics (diabetes, hypertension, hyperlipidemia and prior myocardial infarction). No significant differences were found in the major adverse cardiac and cerebrovascular event (MACCEs) rates between the two groups (1.7% in the stroke group vs. 1.4% in the non-stroke group; p=0.06). Diabetes mellitus, triple vessel CAD, number of diseased vessels, chronic total occlusion and previous myocardial infarction were independent predictors of MACCE in patients with prior stroke undergoing PCI.
Answer: This study demonstrates that, in daily clinical practice, PCI can be provided safely and with good results to patients with a prior ischemic stroke (≥ 3 months).

Ex Output:

Is prior ischemic stroke associated with worse clinical outcomes in patients undergoing percutaneous coronary intervention?