Adaptive and innate immune mechanisms in cardiac fibrosis complicating pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a syndrome diagnosed by increased mean pulmonary artery (PA) pressure and resistance and normal pulmonary capillary wedge pressure. PAH is characterized pathologically by distal pulmonary artery remodeling, increased pulmonary vascular resistance, and plexiform lesions (PLs). Right ventricular fibrosis and hypertrophy, leading to right ventricular failure, are the main determinants of mortality in PAH. Recent work suggests that right ventricular fibrosis results from resident cardiac fibroblast activation and conversion to myofibroblasts, leading to replacement of contractile cardiomyocytes with nondistensible tissue incapable of conductivity or contractility. However, the origins, triggers, and consequences of myofibroblast expansion and its pathophysiological relationship with PAH are unclear. Recent advances indicate that signals generated by adaptive and innate immune cells may play a role in right ventricular fibrosis and remodeling. This review summarizes recent insights into the mechanisms by which adaptive and innate immune signals participate in the transition of cardiac fibroblasts to activated myofibroblasts and highlights the existing gaps of knowledge as relates to the development of right ventricular fibrosis.

[Retracted] Curcumin Improves Pulmonary Hypertension Rats by Regulating Mitochondrial Function

“…As for PHA-related research fields, it has been reported that caspase-1 can regulate inflammatory factors and participate in the occurrence and development of PHA [ 28 ]. IL-1 can mediate the recruitment of macrophages around pulmonary vessels in mice, promote the abnormal proliferation of PASMCs, and cause pulmonary vascular remodeling, which is closely related to the disease progression of PHA [ 29 , 30 ]. Curcumin could inhibit the secretion of IL-1 by inhibiting NLRP3 inflammasome, thus playing an anti-inflammatory role.…”

Airway Remodeling in Feline Lungs

“…Pulmonary artery remodeling is known to be associated with increased pulmonary vascular resistance, which can lead to cardiac fibrosis (Siamwala et al, 2020); this could explain the cardiac interstitial fibrosis detected in the heart of the cases examined.…”

Central Role of Dendritic Cells in Pulmonary Arterial Hypertension in Human and Mice

“…A large proportion of the CD45+ hematopoietic cells appeared to be neither T cells, B cells nor DCs, but might be macrophages or monocytes, since these cells comprise a large population in the heart, both in health and disease (reviewed in [ 34 , 35 ]). Macrophages are implicated in PAH [ 25 , 28 ], possibly by inflammasome-dependent secretion of pro-inflammatory cytokines such as IL-1β and IL-18 [ 36 , 37 ], which are increased in serum of PAH patients [ 15 ]. Interestingly, it has been found in mice that A20-deficient macrophages show spontaneous inflammasome activity and IL-1β secretion [ 38 , 39 ].…”