The development and progression of pulmonary hypertension lesions involve continuous remodeling of the arterial wall, including the extracellular matrix components. The integrity of the internal elastic lamina may represent a barrier to cell migration and formation of intimal proliferative lesions. Some patients with congenital cardiac shunts develop precocious intimal occlusive lesions,whereas others evolve with isolated medial hypertrophy. We studied the 2-D and 3-D morphology of the internal elastic lamina of peripheral pulmonary arteries to search for any difference regarding the type of histological lesion. Fifteen lung biopsies collected for diagnostic purposes from patients with congenital shunts and 6 control lungs (mean ages, 15.8 and 14.7 mo) were studied using the confocal laser scanning microscope, under predetermined conditions of laser intensity, brightness and contrast. We measured the thickness of the internal elastic lamina and determined the number of gaps and projections of elastic tissue towards the medial and intimal layers. The mean internal elastic lamina thickness was significantly higher in arteries from cases with isolated medial hypertrophy when compared with controls and to those with proliferative lesions (P < .05). The number of gaps of the internal elastic lamina was higher in arteries >100 m in diameter from the group with intimal lesions when compared to the cases presenting with isolated hypertrophy, but did not differ from the controls. There was a positive linear correlation between the external arterial diameter and the thickness of the internal elastic lamina (r ‫؍‬ .74, P < .001) in cases presenting isolated medial hypertrophy. The increased thickness and smaller number of gaps of the internal elastic lamina may act as a barrier that prevents smooth muscle cell migration in patients with pulmonary hypertension without intimal proliferative lesions. On the other hand, a greater number of gaps does not represent, by itself, unrestrained migration, because controls also showed fenestrated laminae.

Cardiomyocyte apoptosis and proliferation occur in the majority of patients with idiopathic-dilated cardiomyopathy. High numbers of apoptotic cardiomyocytes and apoptotic interstitial cells are significantly related to a bad late outcome after partial left ventriculectomy.

Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post-infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination, LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and −dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akt1/VEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be dependent on the maintenance of phototherapy. Long-term studies with LLLT application are needed to establish whether these effects ultimately translate into improved cardiac remodeling.

Here we present the application of our adeno-associated virus (AAV2) vector where transgene expression is driven by a synthetic, p53-responsive promoter, termed PG, used to supply human vascular endothelial growth factor-A165 (VEGF-A). Thus, p53 is harnessed to promote the beneficial expression of VEGF-A encoded by the AAVPG vector, bypassing the negative effect of p53 on HIF-1α which occurs during cardiac hypertrophy. Wistar rats were submitted to pressure overload induced by thoracic aorta coarctation (TAC) with or without concomitant gene therapy (intramuscular delivery in the left ventricle). After 12 weeks, rats receiving AAVPG-VEGF gene therapy were compared to those that did not, revealing significantly improved cardiac function under hemodynamic stress, lack of fibrosis and reversal of capillary rarefaction. With these functional assays, we have demonstrated that application of the AAVPG-VEGF vector under physiologic conditions known to stimulate p53 resulted in the preservation of cardiac performance.

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