Abstract-The transient receptor potential vanilloid (TRPV1) channels expressed in sensory afferent fibers innervating the heart may be activated by protons or endovanilloids released during myocardial ischemia (MI), leading to angina. Although our previous in vitro data indicate that TRPV1 activation may preserve cardiac function after ischemiareperfusion injury, the underlying mechanisms are largely unknown. To test the hypothesis that TRPV1 modulates inflammatory and early remodeling processes to prevent cardiac functional deterioration after myocardial infarction, TRPV1-null mutant (TRPV1) and wild-type (WT) mice were subjected to left anterior descending coronary ligation or sham operation. The infarct size was greater in TRPV1 Ϫ/Ϫ than in WT mice (PϽ0.001) 3 days after MI, and the mortality rate was higher in TRPV1 Ϫ/Ϫ than in WT mice (PϽ0.05) 7 days after MI. The levels of plasma cardiac troponin I; cytokines, including tumor necrosis factor-␣, interleukin-1␤, and interleukin-6; chemokines, including monocyte chemoattractant protein-1 and macrophage inflammatory protein-2; and infiltration of inflammatory cells, including neutrophils, macrophages, and myofibroblasts; as well as collagen contents, were greater in TRPV1Ϫ/Ϫ than in WT mice (PϽ0.05) in the infarct area on days 3 and 7 after MI. Changes in left ventricular geometry led to increased end-systolic and -diastolic diameters and reduced contractile function in TRPV1Ϫ/Ϫ compared with WT mice. These data show that TRPV1 gene deletion results in excessive inflammation, disproportional left ventricular remodeling, and deteriorated cardiac function after MI, indicating that TRPV1 may prevent infarct expansion and cardiac injury by inhibiting inflammation and abnormal tissue remodeling. tor is a ligand-gated nonselective cation channel, primarily expressed in sensory nerves innervating the heart and blood vessels. 1,2 TRPV1 may function as a molecular integrator of multiple chemical and physical stimuli, including protons, noxious heat, endovanilloids, and capsaicin. 3,4 Myocardial ischemia causes the release of protons and bradykinin, which may activate or sensitize TRPV1 expressed in cardiac sensory nerve terminals, including unmyelinated C-fibers and thinly myelinated A␦-fibers, to cause angina. 5,6 Indeed, ischemic stimulation of cardiac afferent nerves has been shown to be mediated by activation of TRPV1. 1 Using the isolated, perfused Langendorff heart preparation, we showed that TRPV1 protects the heart from postischemic reperfusion injury possibly via increasing substance P release from sensory nerve terminals. 7 Moreover, TRPV1 contributes to the beneficial effects of preconditioning of the heart against ischemia-reperfusion injury via triggering the release of substance P and/or calcitonin gene-related peptide. 8 It has been shown that patients with preinfarction angina have a better prognosis after acute infarction than those without, a phenomenon ascribed to ischemic preconditioning. 9 However, it is unknown whether TRPV1, a molecular transmitt...

SummaryBackground: Coronary angioscopy in acute myocardial infarction has frequently revealed disrupted yellow lesions. Furthermore, postmortem studies have demonstrated that these lesions have thin collagenous caps with underlying lipid-rich cores.Hypothesis: We hypothesized that the yellow color is due to visualization of reflected light from the lipid-rich yellow core through a thin fibrous cap. Thus, quantification of yellow color saturation may estimate plaque cap thickness and identify vulnerable plaques.Methods: To test this hypothesis, the feasibility of detecting cap thickness was tested using both a model of lipid-rich plaque and human atherosclerotic plaque. The model was constructed by injecting a yellow beta-carotene-lipid emulsion subendothelially into normal bovine aorta. Human plaque was obtained from cadaver aorta. Digitized images were obtained by angioscopy, and percent yellow saturation was analyzed using a custom computer program. Plaque cap thickness was measured by planimetry of digitized images on stained tissue

Thus, ablation of TRPV1 markedly enhances post-MI fibrosis and impairs myocardial contractile performance, leading to increased propensity of functional heart failure and mortality possibly via stimulation of the transforming growth factor-beta-Smad2 signaling pathway. These data indicate that TRPV1 plays a protective role in MI healing and regeneration.

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