盐胁迫下小麦苗叶片吡咯-5-羧酸还原酶活性和游离脯氨酸积累

受NaCl、KCl或MsCl_2胁迫的小麦幼苗,当外部溶液的渗透势由—160 kPa下降到—900 kPa时,叶片吡咯—5—羧酸还原酶(PSC)活性增高;渗透势由—900 kPa降低到—1500kPa,酶活性下降;胁迫 1d和 2d的幼苗,还原酶活性显著增加;3～6d酶活性无大变化。游离脯氨酸含量随溶液渗透势下降和培养时间的延长而提高。胁迫解除后酶活性和脯氨酸含量均降低。受NcCl胁迫义在ABA影响下的幼苗,P5C还原酶活性和脯氨酸含量高于仅受NaCl胁迫的幼苗。     

A one-step assay for pyrroline-5-carboxylate synthase using a short AG1-X8 column

A rapid and simple method for assay of pyrroline-5-carboxylate synthase is presented. In this method, the incubation is terminated by raising the pH of incubation mixture to 10, and [14C]pyrroline 5-carboxylate produced from the substrate, [14C]glutamate, is first converted quantitatively to [14C]proline by reduction with NaBH4 at pH 10 and then the proline is allowed to pass through column of AG1-X8 anion exchanger under the conditions where the glutamate is completely retained by the column. Radioactive counting of the eluate gives the synthase activity. The entire procedure takes only one hour.     

Genetic analysis of Pycr1 and Pycr2 in mice

The final step in proline biosynthesis is catalyzed by three pyrroline-5-carboxylate reductases, PYCR1, PYCR2, and PYCR3, which convert pyrroline-5-carboxylate (P5C) to proline. Mutations in human PYCR1 and ALDH18A1 (P5C Synthetase) cause Cutis Laxa (CL), whereas mutations in PYCR2 cause hypomyelinating leukodystrophy 10 (HLD10). Here, we investigated the genetics of Pycr1 and Pycr2 in mice. A null allele of Pycr1 did not show integument or CL-related phenotypes. We also studied a novel chemically-induced mutation in Pycr2. Mice with recessive loss-of-function mutations in Pycr2 showed phenotypes consistent with neurological and neuromuscular disorders, including weight loss, kyphosis, and hind-limb clasping. The peripheral nervous system was largely unaffected, with only mild axonal atrophy in peripheral nerves. A severe loss of subcutaneous fat in Pycr2 mutant mice is reminiscent of a CL-like phenotype, but primary features such as elastin abnormalities were not observed. Aged Pycr2 mutant mice had reduced white blood cell counts and altered lipid metabolism, suggesting a generalized metabolic disorder. PYCR1 and -2 have similar enzymatic and cellular activities, and consistent with previous studies, both were localized in the mitochondria in fibroblasts. Both PYCR1 and -2 were able to complement the loss of Pro3, the yeast enzyme that converts P5C to proline, confirming their activity as P5C reductases. In mice, Pycr1; Pycr2 double mutants were sub-viable and unhealthy compared to either single mutant, indicating the genes are largely functionally redundant. Proline levels were not reduced, and precursors were not increased in serum from Pycr2 mutant mice or in lysates from skin fibroblast cultures, but placing Pycr2 mutant mice on a proline-free diet worsened the phenotype. Thus, Pycr1 and -2 have redundant functions in proline biosynthesis, and their loss makes proline a semi-essential amino acid. These findings have implications for understanding the genetics of CL and HLD10, and for modeling these disorders in mice.     

Alterations in the activities of the enzymes of proline metabolism in Ragi (Eleusine coracana) leaves during water stress

Free proline content in Ragi (Eleusine coracana) leaves increased markedly (6 to 85 fold) as the degree of water stress, created by polyethylene gylcol treatment, was prolonged There was also a marginal increase in soluble proteins in the stressed leaves as compared to that in the controls. Water stress stimulated the activities of ornithine aminotransferase and pyrroline-5-carboxylate reductase, the enzymes of proline biosynthesis and markedly inhibited the enzymes involved in proline degradation viz., proline oxidase and pyrroline-5-carboxylate dehydrogenase. These results suggest that increase in free proline content of Ragi leaves could be due to enhanced activities of the enzymes synthesizing proline but more importantly due to severe inhibition of the enzymes degrading proline. These observations establish for the first time, the pathway of proline metabolism in plants by way of detection of the activities of all the enzymes involved and also highlight the role of these enzymes in proline accumulation during water stress.     

Metabolic implications of stress-induced proline accumulation in plants

In many plants, free proline accumulates in response to the imposition of a wide range of biotic and abiotic stresses. Controversy has surrounded the extent to which this shift in nitrogen metabolism benefits plants under adverse environmental conditions. Most attempts to account for the phenomenon have focused on the ability of proline to mediate osmotic adjustment, stabilise subcellular structures and scavenge free radicals. However, often the cytoplasmic pool of free proline even after the imposition of stress is insufficient size to account for pronounced biophysical effects.Alternatively, selective preservation of this stress-induced response may relate to endpoints other than simply augmenting the cellular pool of free proline. Proline accumulation may reduce stress-induced cellular acidification or prime oxidative respiration to provide energy needed for recovery. High levels of proline synthesis during stress may maintain NAD(P)+/NAD(P)H ratios at values compatible with metabolism under normal conditions. Consideration of the cofactor preference of plant 1-pyrroline-5-carboxylate (P5C) reductase as well as the in vivo concentrations of the two pyridine nucleotide cofactors and their respective redox ratios suggests that even a small increase in proline biosynthesis might have a large impact on the level of reduction of the cellular NADP pool. The increased NADP+/NADPH ratio mediated by proline biosynthesis is likely to enhance activity of the oxidative pentose phosphate pathway. This would provide precursors to support the demand for increased secondary metabolite production during stress as well as nucleotide synthesis accompanying the accelerated rate of cell division upon relief from stress, when oxidation of proline is likely to provide an important energy source for ADP phosphorylation. Thus, the extreme sensitivity of the metabolic processes of proline synthesis and degradation themselves may be of benefit by regulating metabolic processes adversely affected by stress. This viewpoint is supported by consideration of other physiological phenomena not directly related to stress responses, but in which proline metabolism may also play a regulatory role.A mechanism is proposed whereby the interconversions of proline and P5C in different cell types and the associated transfer of redox potential between tissues may constitute a form of metabolic signalling within higher plants. Stress-related alterations in proline metabolism may impinge on systems of redox control of plant gene expression.     

A new technique of coronary artery ligation: Experimental myocardial infarction in rats in vivo with reduced mortality

In vivo models of myocardial infarction following coronary artery ligation in the rat still suffer from high early mortality and a low rate of success of myocardial infarction. This study investigated the possibility of reducing early mortality and increasing the rate of myocardial infarction by modifications of surgical techniques. Eighteen rats were divided into two groups: normal control (3 rats) and ligation (15 rats). The major modifications of surgical techniques used in this study include: (1) no exteriorization of the heart, (2) ligation of the origins of the branches rather than the main trunk of the left coronary artery, (3) removal of air from the chest after closure, (4) supplying oxygen immediately after extubation. Following surgery, the rats recovered uneventfully and 11 rats were alive after 16 weeks. One rat, with a large myocardial infarction, died 2 h after surgery. Early mortality (during surgery and 1 week after surgery) was 6.7% with a success rate of myocardial infarction of 85%. The left ventricle in the ligation group showed significant dilation relative to normal and shamoperated control hearts (317% of control hearts, p < 0.001). However, myocardial mass did not increase. The average infarct size was 33%. These results demonstrate that a reduction in early mortality and an increased success rate of myocardial infarction can be achieved by modifications of surgical techniques.     

Alteration of collagenous protein profile in congestive heart failure secondary to myocardial infarction

The rat model of myocardial infarction is characterized by progressive cardiac hypertrophy and failure. Rats with infarcts greater than 30% of the left ventricle exhibited early and moderate, stages of heart failure 4 and 8 weeks after the occlusion of the left coronary artery, respectively. As heart failure is usually associated with remodeling of the extracellular matrix, a histological and biochemical study of cardiac collagenous proteins was carried out using failing hearts. Total collagen content in the right ventricle increased at 2, 4, and 8 weeks following occlusion of the left coronary artery whereas such a change in viable left ventricle was seen after 4 and 8 weeks. Total cardiac hydroxyproline concentration was increased in both right and left ventricular samples from the infarcted animals when compared to those of control; this increase was due to elevation of pepsin-insoluble collagen fraction. The myocardial noncollagenous/collagenous protein ratio was decreased in experimental right and left ventricular samples when compared to control samples. These findings suggest that an increase in cross-linking of cardiac collagen as well as disparate synthesis of collagenous and noncollagenous proteins occurs in this model of congestive heart, failure.     

Changes in fatty acid compositions of myocardial lipids in rats with heart failure following myocardial infarction

Changes in fatty acid composition of myocardial lipids were examined in rats with heart failure following myocardial infarction. Left ventricular systolic pressure (LVSP) was decreased and left ventricular end-diastolic pressure (LVEDP) was elevated 24 h, 1 and 12 weeks after left coronary artery ligation (CAL), suggesting the development of heart failure at these periods in this model. Hearts were isolated 24 h, 1 week and 12 weeks after the operation. Myocardial lipids in the infarcted scar tissue, non-infarcted remaining left ventricle including interseptum and right ventricle were separated into phospholipid (PL), triacylglycerol (TG), diacylglycerol (DAG) and free fatty acid (FFA) fractions. In the scar tissue PL content markedly decreased whereas TG, DAG and FFA contents increased 24 h after CAL. Despite a marked decrease in constituted fatty acids of PL fraction in the scar tissue the percentage of arachidonic acid in PL was elevated 12 weeks after CAL, suggesting that release of arachidonic acid during PL degradation was suppressed. In the non-infarcted viable left ventricle PL content remained unchanged throughout the experiment whereas TG, DAG and FFA contents were elevated 24 h after CAL. Despite no changes in PL and other lipid contents in the non-infarcted tissue the percentage of linoleic acid in PL was reduced and that of docosahexaenoic acid in PL was elevated 12 weeks after CAL. Our findings showed that myocardial lipid composition of the non-infarcted left ventricle was altered only in an early stage of the development of heart failure and fatty acid compositions of PL was exchanged in a late stage of the development of heart failure. The exchange may be related to cardiac dysfunction or myocardial remodelling in the rat with heart failure.     

Changes of collagen metabolism predict the left ventricular remodeling after myocardial infarction

Objectives: To analyze the predictive value of cardiac collagen metabolism “in vivo" in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI). Design: Forty-five patients (age 66 ± 8.27) underwent biochemical analysis for cardiac collagen metabolism (groups A, B and C); 30 patients with their first MI were treated with successful PCI (group A; n = 30), group B (n = 5) were MI patients with unsuccessful PCI. Group C were patients without MI (n = 10), they underwent elective diagnostic coronary angiography only. The collagen metabolism was analyzed in acute and subacute MI phases by using serum blood markers: the carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP) and carboxy-terminal telopeptide of type I collagen (ICTP). Furthermore, the ejection fraction (EF) and left ventricular end-diastolic volume maximal changes in the course of 6 months were measured by echocardiography. Results: A significant increase of both PICP and PIIINP on day 4 following MI was detected. Furthermore, PICP and PIIINP level assessed on the 30th day was significantly higher in the PCI unsuccessful group versus successful group. PICP level on day 4 above 110 ug/l and PIIINP level above 4 ug/l was significantly often found in the subgroup of patients with the EF improvement less than 10% or worsening and with significant left ventricular dilatation during 6 months follow-up. Cardiac catheterization itself does not affect collagen metabolism. Conclusion: We concluded that collagen metabolism markers enable to study in vivo the MI healing and to predict left ventricular functional and volume changes.     

Effects of myocardial ischemia/reperfusion injury on plasma metabolomic profile during aging

BackgroundHeart disease is a frequent cause of hospitalization and mortality for elderly patients. A common feature of both heart disease and aging itself is the involvement of metabolic organ alterations ultimately leading to changes in circulating metabolite levels. However, the specific contribution of aging and ischemic injury to the metabolic dysregulation occurring in older adults with ischemic heart disease is still unknown.AimTo evaluate the effects of aging and ischemia/reperfusion (I/R) injury on plasma metabolomic profiling in mice.MethodsYoung and aged mice were subjected to a minimally invasive model of I/R injury or sham operation. Complete evaluation of cardiac function and untargeted plasma metabolomics analysis were performed.ResultsWe confirmed that aged mice from the sham group had impaired cardiac function and augmented left ventricular (LV) dimensions compared to young sham‐operated mice. Further, we found that ischemic injury did not drastically reduce LV systolic/diastolic function and dyssynchrony in aged compared to young mice. Using an untargeted metabolomics approach focused on aqueous metabolites, we found that ischemic injury does not affect the plasma metabolomic profile either in young or old mice. Our data also demonstrate that age significantly affects circulating metabolite levels (predominantly amino acids, phospholipids and organic acids) and perturbs several pathways involved in amino acid, glucid and nucleic acid metabolism as well as pyridoxal‐5′‐phosphate salvage pathway in both sham and ischemic mice.ConclusionsOur approach increases our understanding of age‐associated plasma metabolomic signatures in mice with and without heart disease excluding confounding factors related to metabolic comorbidities.     

Relationship between time of day and periprocedural myocardial infarction after elective angioplasty

Objectives: To test if the time of day significantly influences the occurrence of type 4A myocardial infarction in elective patients undergoing percutaneous coronary intervention (PCI).

Background: Recent studies have suggested an influence of circadian rhythms on myocardial infarction size and mortality among patients with ST-elevation myocardial infarction. The aim of the study is to investigate whether periprocedural myocardial infarction (PMI) is influenced by the time of day in elective patients undergoing PCI.

Methods: All consecutive patients undergoing elective PCI between 2007 and 2011 at our institutions with known post-interventional troponin were retrospectively included. Patients (n?=?1021) were divided into two groups according to the starting time of the PCI: the morning group (n?=?651) between 07:00 and 11:59, and the afternoon group (n?=?370) between 12:00 and 18:59. Baseline and procedural characteristics as well as clinical outcome defined as the occurrence of PMI were compared between groups. In order to limit selection bias, all analyses were equally performed in 308 pairs using propensity score (PS) matching.

Results: In the overall population, the rate of PMI was statistically lower in the morning group compared to the afternoon group (20% vs. 30%, p?<?0.001). This difference remained statistically significant after PS-matching (21% vs. 29%, p?=?0.03). Multivariate analysis shows that being treated in the afternoon independently increases the risk for PMI with an odds ratio of 2.0 (95%CI: 1.1–3.4; p?=?0.02).

Conclusions: This observational PS-matched study suggests that the timing of an elective PCI influences the rate of PMI.     

Differential cytokine expression in myocytes and non-myocytes after myocardial infarction in rats

The proinflammatory cytokines interleukin (IL)-1 and IL-6 are increased after acute myocardial infarction (MI). Moreover, serum IL-6 level is elevated after MI, but has also been associated with heart failure. In the present study, heart function was monitored in a rat model of chronic MI. Cytokine expression in the infarcted and non-infarcted myocardium as well as in hearts of sham-operated controls was measured by the ribonuclease-protection assay. To identify the cells contributing to the increased cytokine expression, we further analyzed myocytes and non-myocytes isolated in the acute phase as well as during congestive heart failure (CHF) after MI. There was a strong induction in cytokine expression in the myocytes of the infarct area 6 h after MI. In the non-infarcted myocardium, cytokine expression increased only slightly in the non-myocytes after 6 h. This was not different from sham-operated controls and may, therefore, be induced by stress and catecholamines. In CHF, however, cytokine expression level in myocytes was normal. It increased slightly but significantly in the non-myocytes 4 and 8 weeks after MI. In conclusion, we suggest that pro-inflammatory cytokines, produced by the ischemic myocytes may be involved in the initiation of wound healing of the necrotic area, whereas the effect of pro-inflammatory cytokines in CHF, if any, seems not to be crucial.     

Decreased plasma nesfatin-1 levels in patients with acute myocardial infarction

Nesfatin-1 is a novel anorexigenic hormone which has close relationship with diabetes, obese, anorexia nervosa, psychiatric disorders and neurogenic diseases. The aim of our study was to evaluate levels of plasma nesfatin-1 among patients presenting with coronary artery disease and the correlation between nesfatin-1 levels and other clinical parameters. Fasting plasma levels of nesfatin-1 were tested in 48 acute myocardial infarction (AMI) patients, 74 stable angina pectoris (SAP) patients and 34 control subjects. All of them were examined by coronary angiography. The severity of coronary atherosclerosis was assessed using the Gensini score. Plasma nesfatin-1 levels were significantly lower in AMI group than SAP group or control group (0.91 ± 0.08 ng/mL vs. 0.98 ± 0.19 ng/mL and 1.09 ± 0.39 ng/mL, respectively, P < 0.05). In AMI patients, plasma nesfatin-1 levels were negatively correlated with high-sensitivity C-reactive protein, neutrophil% or Gensini scores. Such information implies that lower nesfatin-1 concentration may play a very important role in the development of AMI.     

Associations of serum high-sensitivity C-reactive protein and prealbumin with coronary vessels stenosis determined by coronary angiography and heart failure in patients with myocardial infarction

BackgroundTo explore the associations of serum high-sensitivity C-reactive protein (hs-CRP) and prealbumin (PAB) with the number of diseased coronary vessels, degree of stenosis and heart failure in patients with myocardial infarction (MI).MethodsA total of 39 MI patients treated in the Cardiology were selected as the observation group, and another 41 patients with normal results of coronary angiography during the same period were selected as the control group. The general data of patients were recorded in detail, the content of serum hs-CRP and PAB in the peripheral blood was detected, and the number of diseased coronary vessels and the degree of stenosis were detected via coronary angiography.ResultsCompared with those in control group, the blood pressure and heart rate significantly rose, the content of indexes related to the severity of MI were significantly increased, the content of hs-CRP was significantly increased, and the content of PAB was significantly decreased in observation group. Hs-CRP was positively correlated with the number of diseased coronary vessels, degree of stenosis and heart failure in patients, but PAB was negatively correlated with the above factors. The survival rate of MI patients with high content of hs-CRP was obviously lower than that of patients with low content of hsCRPConclusionsSerum hs-CRP and PAB are closely associated with the number of diseased coronary vessels, degree of stenosis and heart failure in MI patients.     

TLR3 contributes to persistent autophagy and heart failure in mice after myocardial infarction

Toll‐like receptors (TLRs) are essential immunoreceptors involved in host defence against invading microbes. Recent studies indicate that certain TLRs activate immunological autophagy to eliminate microbes. It remains unknown whether TLRs regulate autophagy to play a role in the heart. This study examined this question. The activation of TLR3 in cultured cardiomyocytes was observed to increase protein levels of autophagic components, including LC3‐II, a specific marker for autophagy induction, and p62/SQSTM1, an autophagy receptor normally degraded in the final step of autophagy. The results of transfection with a tandem mRFP‐GFP‐LC3 adenovirus and use of an autophagic flux inhibitor chloroquine both suggested that TLR3 in cardiomyocytes promotes autophagy induction without affecting autophagic flux. Gene‐knockdown experiments showed that the TRIF‐dependent pathway mediated the autophagic effect of TLR3. In the mouse model of chronic myocardial infarction, persistent autophagy was observed, concomitant with up‐regulated TLR3 expression and increased TLR3‐Trif signalling. Germline knockout (KO) of TLR3 inhibited autophagy, reduced infarct size, attenuated heart failure and improved survival. These protective effects were abolished by in vivo administration of an autophagy inducer rapamycin. Similar to the results obtained in cultured cardiomyocytes, TLR3‐KO did not prevent autophagic flux in mouse heart. Additionally, this study failed to detect the involvement of inflammation in TLR3‐KO‐derived protection, as wild‐type and TLR3‐KO hearts were comparable in inflammatory activity. It is concluded that up‐regulated TLR3 expression and signalling contributes to persistent autophagy following MI, which promotes heart failure and lethality.     

A deletion in the nitrate high affinity transporter NRT2.1 alters metabolomic and transcriptomic responses to Pseudomonas syringae

A deletion in the high affinity nitrate trasporter NRT2.1 in Arabidopsis results in a reduced susceptibility to Pseudomonas syringae by two different mechanisms, the SA priming and an interference in the effector triggered susceptibility. In the present research we further characterized the metabolic and genetic profiles of the mutant nrt2 in the interaction with P. syringae. Despite the priming found in the SA-dependent pathway, the metabolic changes in nrt2 compared with wild-type plants are more remarkable prior infection. This is associated mainly to a pre-existing over representation of signals attributed to aromatic amino acids and phenylpropanoids in the nrt2. Genomic analysis confirms the implication of aromatic aminoacids and phenylpropanoids, but additionally, suggests a new role in ribosomal proteins as the major changes observed in nrt2 upon infection by the bacterium.     

Leaf position-dependent changes in proline,pyrroline-5-carboxylate reductase activity and water relations under salt-stress in genetically stable salt-tolerant somaclones ofBrassica juncea L.

The magnitude of the effect of salt stress on proline content, pyrroline-5-carboxylate (P5C) reductase activity and water relations was found to be leaf position dependent in an advance generation (R4) of twoBrassica juncea L. somaclones (SR-2 and SR-3) selected in vitro for NaCl-tolerance and the parent cv. Prakash. Free proline content and P5C reductase activity increased with increase in salt stress in all the lines but at different rates; the maximum increase being in the SR-3 derived somaclonal line. At 100 mM NaCl, SR-3 showed a nearly 19 fold increase in proline content compared to a 4–5 fold increase in the other two genotypes. The proline level and P5C reductase activity of the first (youngest) leaf was higher than in the other leaves and decreased linearly with increase in age of the leaf in all the lines. The relationship between relative water content and osmotic potential of the leaves at different positions also varied. The results indicate that a significant effect of salt may appear non-significant if the position of the leaves is not taken into account while sampling.     

Metabolism of vitamin A in the heart increases after a myocardial infarction

The supply of vitamin A to the myocardium by storage organs during increased oxidative stress subsequent to myocardial infarction (MI) was examined in hemodynamically assessed rats using compartment analysis of a radio-labeled vitamin A. 3H-Vitamin A was injected into two groups of rats: an MI group and a control group. There were no differences in the plasma or myocardial content of total vitamin A (unlabeled + labeled) between the two groups. However, the proportion of 3H-vitamin A was greater in the myocardium as well as plasma of MI rats. Rats with MI also had significantly lower 3H-vitamin A levels in liver and kidney than sham controls. The greatest difference in vitamin A content was in the concentrations of 3H-labeled storage forms of vitamin A in the liver of MI animals. Activity of bile salt-dependent retinyl ester hydrolase, an enzyme responsible for hydrolyzing vitamin A storage forms, was significantly increased in the liver of MI animals. These data indicate that analysis of plasma concentrations of vitamin A to ascertain links to cardiac conditions may be inappropriate. Specifically, during MI, increased amounts of vitamin A are mobilized from the liver to the heart without changing plasma concentrations. This is facilitated by an increase in the activity of an enzyme that hydrolyzes vitamin A storage forms.     

Cardiotrophin-1: Expression in experimental myocardial infarction and potential role in post-MI wound healing

Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been shown to be elevated in the serum of patients with ischemic heart disease and valvular heart disease, and induces cardiomyocyte hypertrophy in vitro. We investigated expression of CT-1 in post-MI rat heart and the effect of CT-1 on cultured primary adult rat cardiac fibroblasts. Elevated CT-1 expression was observed in the infarct zone at 24 h and continued through 2, 4 and 8 weeks post-MI, compared to sham-operated animals. CT-1 induced rapid phosphorylation of Jak1, Jak2, STAT1, STAT3, p42/44 MAPK and Akt in cultured adult cardiac fibroblasts. CT-1 induced cardiac fibroblast protein synthesis and proliferation. Protein and DNA synthesis were dependent on activation of Jak/STAT, MEK1/2, PI3K and Src pathways as evidenced by decreased ³H-leucine and ³H-thymidine incorporation after pretreatment with AG490, PD98059, LY294002 and genistein respectively. Furthermore, CT-1 treatment increased procollagen-1-carboxypropeptide (P1CP) synthesis, a marker of mature collagen synthesis. CT-1 induced cell migration of rat cardiac fibroblasts. Our results suggest that CT-1, as expressed in post-MI heart, may play an important role in infarct scar formation and ongoing remodeling of the scar. CT-1 was able to initiate each of the processes considered important in the formation of infarct scar including cardiac fibroblast migration as well as fibroblast proliferation and collagen synthesis. Further work is required to determine factors that induce CT-1 expression and interplay with other mediators of cardiac infarct wound healing in the setting of acute cardiac ischemia and chronic post-MI heart failure.