Beneficial Effects of Galectin-3 Blockade in Vascular and Aortic Valve Alterations in an Experimental Pressure Overload Model

Abstract

Galectin-3 (Gal-3) is involved in cardiovascular fibrosis and aortic valve (AV) calcification. We hypothesized that Gal-3 pharmacological inhibition with modified citrus pectin (MCP) could reduce aortic and AV remodeling in normotensive rats with pressure overload (PO). Six weeks after aortic constriction, vascular Gal-3 expression was up-regulated in male Wistar rats. Gal-3 overexpression was accompanied by an increase in the aortic media layer thickness, enhanced total collagen, and augmented expression of fibrotic mediators. Further, vascular inflammatory markers as well as inflammatory cells content were greater in aorta from PO rats. MCP treatment (100 mg/kg/day) prevented the increase in Gal-3, media thickness, fibrosis, and inflammation in the aorta of PO rats. Gal-3 levels were higher in AVs from PO rats. This paralleled enhanced AV fibrosis, inflammation, as well as greater expression of calcification markers. MCP treatment prevented the increase in Gal-3 as well as fibrosis, inflammation, and calcification in AVs. Overall, Gal-3 is overexpressed in aorta and AVs from PO rats. Gal-3 pharmacological inhibition blocks aortic and AV remodeling in experimental PO. Gal-3 could be a new therapeutic approach to delay the progression and the development of aortic remodeling and AV calcification in PO.

Echocardiographic diastolic function evolution in patients with an anterior Q‐wave myocardial infarction: insights from the REVE‐2 study

“…43 Nonetheless, experimental models suggest that blocking Gal-3 pathways may attenuate cardiac fibrosis, vascular remodelling, LV dysfunction, and heart failure onset. 44,45 In this study, higher Gal-3 levels were associated with lower lateral e 0 and septal e 0 , suggesting that Gal-3 may also be related to DD independently of increased congestion. 46,47 Reduced systemic concentrations of ICTP may reflect reduced collagen type I fibre degradation by MMP-1 given that high lysyl oxidase-mediated cross-linking increases the resistance of the fibre to MMP-1 proteolysis.…”

“…fibroblasts, macrophages, myocytes, and renal cells) and may be extracellular, cytoplasmic, or nuclear. 44,45 In this study, higher Gal-3 levels were associated with lower lateral e 0 and septal e 0 , suggesting that Gal-3 may also be related to DD independently of increased congestion. 43 Nonetheless, experimental models suggest that blocking Gal-3 pathways may attenuate cardiac fibrosis, vascular remodelling, LV dysfunction, and heart failure onset.…”

Galectin-3 as a novel biotarget in cardiovascular alterations associated to development of severe aortic stenosis

“…In a recent study, it has been demonstrated that pharmacological Gal-3 inhibition by MCP could delay vascular remodeling and inflammation in a rat model of pressure overload (Fig. 3) 51,56 . Gal-3 inhibition exerts beneficial effects, decreasing aortic tunica media hypertrophy.…”

“…Complementarily, MCP treatment diminishes the expression of the inflammatory markers interleukin-6, interleukin-1β, tumor necrosis factor-α, monocyte chemoattractant protein-1, osteopontin, cd45 and cd68 in pressure-overloaded aortae (Fig. 3) 51,56 . These results suggest that Gal-3 may contribute toward adverse cardiovascular effects in part through an effect on aortic stiffness.…”

“…For collagen quantification (fibrosis), Sirius red staining was performed. Representative immunohistochemistry for cd68 and bone morphogenetic protein 4 are showed as examples of aortic valve inflammation and calcification respectively (from Ibarrola et al, 2017)56 . myocardial biopsies from AS patients18 , reinforcing the key role of this lectin in the inflammatory process and in extracellular matrix remodeling that accompanies the development of AS.…”