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Visual Abstract, Highlights • AAV9 vectors can upregulate Rxfp1 mRNA in murine heart after intravenous injection. • RXFP1 upregulation sensitizes the left ventricle to relaxin-induced inotropy. • RXFP1 overexpression protects heart from ischemia-reperfusion injury., Summary Relaxin is a pleiotropic hormone shown to confer cardioprotection in several preclinical models of cardiac ischemia-reperfusion injury. In the present study, the effects of up-regulating relaxin family peptide receptor 1 (RXFP1) via adeno-associated virus serotype 9 (AAV9) vectors were investigated in a mouse model of myocardial infarction. AAV9-RXFP1 vectors were generated and injected in adult male CD1 mice. Up-regulation of Rxfp1 was confirmed via quantitative polymerase chain reaction, and overexpressing animals showed increased sensitivity to relaxin-induced ventricular inotropic response. Overexpressing animals also demonstrated reduced infarct size and preserved cardiac function 24 hours after ischemia-reperfusion. Up-regulation of RXFP1 via AAV9 vectors has potential therapeutic utility in preventing adverse remodeling after myocardial infarction.

Visual Abstract, Highlights • Acute pericarditis is characterized by an intense inflammatory response involving the pericardium. Although mostly benign in its clinical course, 30% of patients may experience complications (recurrence, treatment failure, cardiac tamponade). • The pathogenesis of pericarditis is poorly understood. The scarcity of animal models might justify the limited understanding of this syndrome and the lack of targeted therapies. • Acute pericarditis is believed to represent a stereotypical response to an acute injury of the pericardium. The NLRP3 inflammasome, through its main product, IL-1β, could play a central role in the clinical manifestations. • A mouse model of acute pericarditis was developed through the intrapericardial injection of zymosan A, leading to the classical features of the inflamed pericardium: pericardial effusion, pericardial thickening, and increased expression of the NLRP3 inflammasome. By inhibiting the NLRP3 inflammasome or IL-1β, the pericardial effusion and thickening and the NLRP3 inflammasome expression were greatly reduced compared with vehicle. • Treatment with IL-1 trap, neutralizing both IL-1β and IL-1α, produced a powerful effect on pericardial inflammation in the experimental pericarditis model., Summary Human samples of patients with chronic pericarditis and appropriate control subjects were stained for the inflammasome components. A mouse model of pericarditis was developed through the intrapericardial injection of zymosan A. Different inflammasome blockers were tested in the mouse model. Patients with pericarditis presented an intensification of the inflammasome activation compared with control subjects. The experimental model showed the pathological features of pericarditis. Among inflammasome blockers, NLRP3 inflammasome inhibitor, anakinra, and interleukin-1 trap were found to significantly improve pericardial alterations. Colchicine partially improved the pericardial inflammation. An intense activation of the inflammasome in pericarditis was demonstrated both in humans and in mice.

Highlights •Pericarditis is the most common disease of the pericardium. Generally self-limiting, pericarditis can be fraught by a significant risk of acute complications and of recurrences. •Prompt diagnosis and appropriate treatment of acute pericarditis may reduce the risk of acute complications and recurrences. •New therapies, such as IL-1 blockers, show promising results in patients with recurrent/refractory pericarditis. •Future studies are needed to deepen the knowledge about pericarditis pathophysiology and provide targeted therapies.

Visual Abstract, Highlights • The effects of UFA on CRF in patients with HFpEF are unknown. • In obese HFpEF patients, UFA consumption analyzed with a validated 24-h dietary recall was positively associated with improved body composition, cardiac diastolic function and greater CRF, measured as peak VO2 at maximal cardiopulmonary exercise testing. Conversely, sugars consumption was associated with worse CRF. • In mice, an isocaloric high-fat diet, high in UFA and low in saturated fat prevented cardiac diastolic dysfunction measured with echocardiography and body weight gain in a model of cardiac dysfunction and obesity induced by Western diet, despite similar total caloric intake. • A high-UFA diet is associated with preservation of CRF in patients with HFpEF and cardiac function in the mouse., Summary Heart failure with preserved ejection fraction (HFpEF) is associated with obesity and, indirectly, with unhealthy diet. The role of dietary components in HFpEF is, however, largely unknown. In this study, the authors showed that in obese HFpEF patients, consumption of unsaturated fatty acids (UFA), was associated with better cardiorespiratory fitness, and UFA consumption correlated with better diastolic function and with greater fat-free mass. Similarly, mice fed with a high-fat diet rich in UFA and low in sugars had preserved myocardial function and reduced weight gain. Randomized clinical trials increasing dietary UFA consumption and reducing sugar consumption are warranted to confirm and expand our findings.