Phenotypic switching prevention and proliferation/migration inhibition of vascular smooth muscle cells by the ruthenium nitrosyl complextrans-[Ru(NO)Cl(cyclam](PF6)2

Abstract

With great potential to maintain VSMC functionality and prevent IH-associated events, cyclamNO might be a promissory drug for several applications in cardiovascular medicine, as in stents.

Oxymatrine suppresses MOVAS proliferation induced by platelet-derived growth factor via G0/G1 arrest

“…After vascular injury, a variety of growth factors, cytokines and chemokines are synthesized and secreted, which can stimulate VSMCs phenotype switching, accelerate VSMCs migration to inner membranes, induce the excessive proliferation of VSMCs and further lead to vascular restenosis [34][35][36]. PDGF, mainly expressed in VSMCs and endothelial cells, promote mitosis and play an important role in the proliferation of VSMCs [6][7][8]37]. The binding of PDGF-BB, a subtype of PDGF released from injured vessels, to its receptor can trigger the activation of downstream and then contribute significantly to VSMCs proliferation [9][10][11][12].…”

“…Thus, inhibition excessive proliferation of VSMCs is one of the important strategies to prevent restenosis after angioplasty. Platelet-Derived Growth Factor (PDGF) is an important regulator that stimulates the proliferation of VSMCs [6][7][8]. The binding of PDGF-BB, a subtype of PDGF, to its receptor triggers the activation of downstream signaling molecules such as Mitogen-Activated Protein Kinases (MAPKs) to promote VSMCs proliferation and growth [9][10][11][12][13].…”

Ruthenium-nitrosyl complexes as NO-releasing molecules, potential anticancer drugs, and photoswitches based on linkage isomerism

“…The diaqua complex formed by NO or NO − liberation could act as a nitrite (NO 2 − ) scavenger, forming the nitro complex trans -[Ru(cyclam)(NO 2 )(OH 2 )] + , which in turn, converts back to the ruthenium nitrosyl complex trans -[Ru(cyclam)(NO)(OH 2 )] 3+ (or trans -[Ru(cyclam)(NO)(OH)] 2+ at physiological pH). 82,151,162,163 As nitrite is one of the major NO x pools in blood, 164 these reactions would constitute a catalytic conversion of nitrite to NO, increasing the efficiency of the mac and tertrammine ruthenium nitrosyls as NO donors (Scheme 5).…”

“…Recently, control of vascular smooth muscle cell growth was mediated by trans -[Ru(cyclam)(NO)Cl](PF 6 ) 2 and the observed long-lasting effect connected with NO release after reduction could protect against the development of intimal hyperplasia (IH – vessel wall thickening), a common complication in vascular remodeling surgery. 163…”

The Structures, Spectroscopic Properties, and Photodynamic Reactions of Three [RuCl(QN)NO]−Complexes (HQN = 8-Hydroxyquinoline and Its Derivatives) as Potential NO-Donating Drugs

“…They are coordinated with (N,N) bidentate ligands forming cationing complexes. The cytotoxicity against tumor cell and their vasodilation effects have been studied [20–25]. Here, three [RuCl 3 (QN)(NO)] − anionic complexes were synthesized using 8-hydroxyquinoline and its derivatives (HQN) as ligands.…”