IL-1RN*2 was significantly associated with SVD. A difference in genetic association between SVD and MVD was also apparent.

Objective: To investigate the relative importance of stent induced arterial stretch and deep injury to the development of in-stent neointima. Setting: Normal porcine coronary arteries Methods: 30 BiodivYsio stents (Biocompatibles) were deployed at a stent to artery ratio of 1.25:1 (a moderate injury) and harvested at 28 days. Multiple serial cross sections were analysed morphometrically and the neointimal areas were correlated with the type and degree of injury. Results: Arterial stretch occurred in 78% of struts (77% of sections) and produced moderate neointimal growth (neointimal area 1.93 (0.13) mm 2 ). Deep injury (rupture of the internal elastic lamina) occurred in 20% of struts (23% of sections) and produced a 1.7-fold increase in neointimal area (3.33 (0.41) mm 2 ) compared with stretch only (p = 0.0002). With even deeper injury (rupture of the external elastic lamina), there was a 2.6-fold increase in neointimal area (5.01 (0.48) mm 2 ) compared with stretch only (p = 0.02). A new injury score, incorporating both stretch and deep injury, correlated with neointimal area (r = 0.60, p < 0.001). Conclusions: Stretch of the coronary artery in a stent is common, and a major contributor to neointima formation, even in the absence of deep injury. Deep injury is, however, a more potent stimulus to neointima formation than stretch. Greater degrees of stretch are associated with thicker neointima. Where neither deep injury nor stretch are seen, the stent has no effect upon the development of neointima. Stents are now used in more than 70% of percutaneous coronary interventions. In-stent restenosis is important because it is common and difficult to treat. It is known from intravascular ultrasound (IVUS) studies that in-stent dimensions and stent length are the main predictors of in-stent restenosis.

From July 1, 1990 to February 28, 1991, 533 consecutive patients with 764 target vessels and 1,000 lesions underwent coronary angioplasty. Procedural success was achieved in 92.3%, untoward (major cardiac) events occurred in 3% (0.8% myocardial infarction, 1.3% emergency coronary bypass grafting and 0.9% both; there were no deaths). An unsuccessful uncomplicated outcome occurred in 4.7%. Lesion analysis using a modified American College of Cardiology/American Heart Association classification system showed that 8% were type A, 47.5% were type B and 44.5% were type C (36% of type B and 11% of type C were occlusions). Angioplasty success was achieved in 99% of type A, 92% of type B and 90% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.01). Untoward events occurred in 1.2% of type A, 1.9% of type B and 2% of type C lesions (p = NS). An unsuccessful uncomplicated outcome occurred in 0% of type A, 6% of type B and 7% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.05). Among the unsuccessful uncomplicated outcome group, occlusion occurred in 49%: 38% of type B and 59% of type C lesions. With B1 and B2 subtypes, success was obtained in 95% and 89.5% and untoward events occurred in 1.5% and 2.3% and an unsuccessful uncomplicated outcome in 3.7% and 8%, respectively. C1 and C2 subtyping showed success in 91% and 86%, untoward events in 1.3% and 6% and an unsuccessful uncomplicated outcome in 7.5% and 8.5%, respectively. Among the 764 vessels, success was obtained in 89.5% and untoward events occurred in 2.5% and an unsuccessful uncomplicated outcome in 8%. Assessment of lesion-vessel combinations showed a less favorable outcome with type C lesions and combinations of A-B, B-C and multiple (more than three lesions) type B and C vessels. Statistical analysis of morphologic factors associated with angioplasty success included absence of (old) occlusion (p less than 0.0001) and unprotected bifurcation lesion (p less than 0.001), decreasing lesion length (p less than 0.003) and no thrombus (p less than 0.03). The only significant factor associated with untoward events was the presence of thrombus (p less than 0.003). Predictors of an unsuccessful uncomplicated outcome included old occlusion (p less than 0.0001) and increasing lesion length (greater than 20 mm) (p less than 0.001), unprotected bifurcation lesion (p less than 0.05) and thrombus (p less than 0.03).

Background-Restenosis after percutaneous coronary intervention remains a serious clinical problem. Progress in local gene therapy to prevent restenosis has been hindered by concerns over the safety and efficacy of viral vectors and the limited efficiency of nonviral techniques. This study investigates the use of adjunctive ultrasound to enhance nonviral gene delivery. Methods and Results-Cultured porcine vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) were transfected with naked or liposome-complexed luciferase reporter plasmid for 3 hours. Ultrasound exposure (USE) for 60 seconds at 1 MHz, 0.4 W/cm 2 , 30 minutes into this transfection period enhanced luciferase activity 48 hours later by 7.5-fold and 2.4-fold, respectively. Luciferase activity after lipofection of ECs was similarly enhanced 3.3-fold by adjunctive USE. USE had no effect on cell viability, although it inhibited VSMC but not EC proliferation. An alternative strategy is single-dose local administration of agents that can modify the vascular response to injury, including local gene therapy. 1 Viral vectors achieve the highest efficiency, but substantial concerns remain over their clinical safety and long-term efficacy. 1 Although relatively safe, nonviral gene delivery, including lipofection, is currently at least 10-fold less efficient. 1 Ultrasound exposure (USE) has been shown to permeabilize plasma membranes and reduce the thickness of the unstirred layer at the cell surface, 2,3 which should encourage DNA entry into cells. Furthermore, many lipofection reagents contain dioleoylphosphatidylethanolamine (DOPE), which encourages DNA "breakout" from endosomes through a physicochemical transition that is known to be accelerated by USE. 4,5 On the basis of these observations, we investigated the hypothesis that USE may enhance transgene expression after naked DNA and/or liposome-mediated transfection of primary vascular cells. Conclusions-Adjunctive Methods Cell Culture and Transfection ConditionsPorcine medial vascular smooth muscle cells (VSMCs) and lumenal endothelial cells (ECs) from the thoracic aorta of Yorkshire White cross pigs aged Ͻ6 months were cultured in DMEM containing 10% porcine serum; EC cultures were supplemented with EC growth factor (20 g/mL; Sigma) and heparin (90 g/mL; Sigma). All transfections were performed for 3 hours at 37°C in 24-well plates with cells at 60% to 70% confluence and were stopped by dilution with 1 mL of fresh culture medium. Naked DNA transfections were performed in 200 L of DMEM containing 10% porcine serum and 7.5 g/mL luciferase plasmid DNA (pGL3; Promega) per well. Lipofections used Promega Tfx-50 (which contains DOPE), according to conditions optimized for VSMCs (200 L of DMEM containing 10% porcine serum; DNA:lipid charge ratio of 4:1; 7.5 g/mL final DNA concentration) and ECs (200 L of serum-free DMEM; DNA:lipid charge ratio 3:1; 5 g/mL final DNA concentration).Thirty minutes after the transfection was begun, USE was performed for 60 seconds with a custom-built, 10-mm-diameter, 1-MHz ...