Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy.

AIM: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder mainly due to mutations in desmosomal genes, characterized by progressive fibro-adipose replacement of the myocardium, arrhythmias, and sudden death. It is still unclear which cell type is responsible for fibro-adipose substitution and which molecular mechanisms lead to this structural change. Cardiac mesenchymal stromal cells (C-MSC) are the most abundant cells in the heart, with propensity to differentiate into several cell types, including adipocytes, and their role in ACM is unknown. The aim of the present study was to investigate whether C-MSC contributed to excess adipocytes in patients with ACM. METHODS AND RESULTS: We found that, in ACM patients' explanted heart sections, cells actively differentiating into adipocytes are of mesenchymal origin. Therefore, we isolated C-MSC from endomyocardial biopsies of ACM and from not affected by arrhythmogenic cardiomyopathy (NON-ACM) (control) patients. We found that both ACM and control C-MSC express desmosomal genes, with ACM C-MSC showing lower expression of plakophilin (PKP2) protein vs. CONTROLS: Arrhythmogenic cardiomyopathy C-MSC cultured in adipogenic medium accumulated more lipid droplets than controls. Accordingly, the expression of adipogenic genes was higher in ACM vs. NON-ACM C-MSC, while expression of cell cycle and anti-adipogenic genes was lower. Both lipid accumulation and transcription reprogramming were dependent on PKP2 deficiency. CONCLUSIONS: Cardiac mesenchymal stromal cells contribute to the adipogenic substitution observed in ACM patients' hearts. Moreover, C-MSC from ACM patients recapitulate the features of ACM adipogenesis, representing a novel, scalable, patient-specific in vitro tool for future mechanistic studies.

Effect of climate change on Alternaria leaf spot of rocket salad and black spot of basil under controlled environment.

Plant responses to elevated CO2 and temperature have been much studied in recent years, but effects of climate change on pathological responses are still largely unknown. The pathosystems rocket (Eruca vesicaria subsp. sativa)--Alternaria leaf spot (Alternaria japonica) and basil (Ocimum basilicum)--black spot (Colletotrichum gloeosporioides) were chosen as models to assess the potential impact of increased CO2 and temperature on disease incidence and severity under controlled environment. Potted plants were grown in phytotrons under 4 different simulated climatic conditions: (1) standard temperature (ranging from 18 degrees to 22 degrees C) and standard CO2 concentration (400 ppm); (2) standard temperature and elevated CO2 concentration (800 ppm); (3) elevated temperature (ranging from 22 degrees to 26 degrees C, 4 degrees C higher than standard) and standard CO2 concentration; (4) elevated temperature and CO2 concentration. Each plant was inoculated with a spore suspension containing 1 x 10(5) cfu/ml of the pathogen. Disease incidence and severity were assessed 14 days after inoculation. Increasing CO2 to 800 ppm showed a clear increment in the percentage of Alternaria leaf spot on rocket leaves compared to standard conditions. Basil plants grown at 800 ppm of CO2 showed increased black spot symptoms compared to 400 ppm. Disease incidence and severity were always influenced by the combination of rising CO2 and increased temperature, compared to standard conditions (400 ppm of CO2 - 22 degrees C). Considering the rising concentrations of CO2 and global temperature, we can assume that this could increase the severity of Alternaria japonica on rocket and Colletotrichum gloeosporioides on basil.