Cigarette smoking is at all-time lows globally, but the use of electronic cigarettes has increased profoundly. Recent reports of electronic cigarette or vaping use-associated lung injury may lead individuals to explore novel methods of nicotine consumption, such as heat-not-burn devices. IQOS from Philip Morris, a heat-not-burn device, became available for purchase in the United States in October 2019. Philip Morris claims that 8.8 million people have abandoned traditional cigarettes in favor of IQOS; however, evidence suggests that it may act as a gateway or complement to cigarette smoking, rather than a replacement. Surveys indicate that 96% of Korean IQOS users also smoke cigarettes, and 45% of Italian users of IQOS had never smoked cigarettes. In the United States, Canada, and England, susceptibility of youth to trying IQOS was slightly lower than electronic cigarettes, but higher than cigarette smoking. Heat-not-burn products produce mainstream and second-hand emissions of harmful chemicals, including nicotine, particulate matter, benzene, acrolein, and tobacco-specific nitrosamines. The levels of these emissions, despite being less than those of traditional cigarettes, are potentially harmful to cardiovascular health. A study of current smokers showed similar acute effects of heat-not-burn tobacco products and traditional cigarettes on heart rate, blood pressure, and arterial stiffness. Rats exposed to IQOS had similar vascular endothelial function impairment to those exposed to cigarettes. Heat-not-burn aerosol exposure of cultured macrophages elicited increased oxidative stress, although less than that induced by cigarette smoke. Further studies are needed to better understand the cardiovascular effects of heat-not-burn tobacco products.

Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases; however, the role of nicotine in the pathogenesis of these diseases is incompletely understood. The purpose of this study was to examine the effects of chronic nicotine inhalation on the development of cardiovascular and pulmonary disease with a focus on blood pressure and cardiac remodeling. Male C57BL6/J mice were exposed to air (control) or nicotine vapor (daily, 12 hour on/12 hour off) for 8 weeks. Systemic blood pressure was recorded weekly by radio-telemetry, and cardiac remodeling was monitored by echocardiography. At the end of the 8 weeks, mice were subjected to right heart catheterization to measure right ventricular systolic pressure. Nicotine-exposed mice exhibited elevated systemic blood pressure from weeks 1 to 3, which then returned to baseline from weeks 4 to 8, indicating development of tolerance to nicotine. At 8 weeks, significantly increased right ventricular systolic pressure was detected in nicotine-exposed mice compared with the air controls. Echocardiography showed that 8-week nicotine inhalation resulted in right ventricular (RV) hypertrophy with increased RV free wall thickness and a trend of increase in RV internal diameter. In contrast, there were no significant structural or functional changes in the left ventricle following nicotine exposure. Mechanistically, we observed increased expression of angiotensin-converting enzyme and enhanced activation of mitogen-activated protein kinase pathways in the RV but not in the left ventricle. We conclude that chronic nicotine inhalation alters both systemic and pulmonary blood pressure with the latter accompanied by RV remodeling, possibly leading to progressive and persistent pulmonary hypertension.

We have previously reported gender differences in ventricular remodeling and development of heart failure using the aortocaval fistula model of chronic volume overload in rats. In contrast to males, female rats exhibited no adverse ventricular remodeling and less mortality in response to volume overload. This gender-specific cardioprotection was lost following ovariectomy and was partially restored using estrogen replacement. However, it is not known if estrogen treatment would be as effective in males. The purpose of this study was to evaluate the structural and functional effects of estrogen in male rats subjected to chronic volume overload. Four groups of male rats were studied at 3 days and 8 wk postsurgery as follows: fistula and sham-operated controls, with and without estrogen treatment. Biochemical and histological studies were performed at 3 days postsurgery, with chronic structural and functional effects studied at 8 wk. Measurement of systolic and diastolic pressure-volume relationships was obtained using a blood-perfused isolated heart preparation. Both fistula groups developed significant ventricular hypertrophy after 8 wk of volume overload. Untreated rats with fistula exhibited extensive ventricular dilatation, which was coupled with a loss of systolic function. Estrogen attenuated left ventricular dilatation and maintained function in treated rats. Estrogen treatment was also associated with a reduction in oxidative stress and circulating endothelin-1 levels, as well as prevention of matrix metalloproteinase-2 and -9 activation and breakdown of ventricular collagen in the early stage of remodeling. These data demonstrate that estrogen attenuates ventricular remodeling and disease progression in male rats subjected to chronic volume overload.

The cardiac extracellular matrix is a complex architectural network that serves many functions, including providing structural and biochemical support to surrounding cells and regulating intercellular signaling pathways. Cardiac function is directly affected by extracellular matrix (ECM) composition, and alterations of the ECM contribute to the progression of heart failure. Initially, collagen deposition is an adaptive response that aims to preserve tissue integrity and maintain normal ventricular function. However, the synergistic effects of proinflammatory and profibrotic responses induce a vicious cycle, which causes excess activation of myofibroblasts, significantly increasing collagen deposition and accumulation in the matrix. Furthermore, excess synthesis and activation of the enzyme lysyl oxidase (LOX) during disease increases collagen cross-linking, which significantly increases collagen resistance to degradation by matrix metalloproteinases (MMPs). In the present study, the aortocaval fistula model of volume overload (VO) was used to determine whether LOX inhibition could prevent adverse changes in the ECM and subsequent cardiac dysfunction. The major findings from this study were that LOX inhibition 1) prevented VO-induced increases in left ventricular wall stress; 2) partially attenuated VO-induced ventricular hypertrophy; 3) completely blocked the increases in fibrotic proteins, including collagens, MMPs, and their tissue inhibitors; and 4) prevented the VO-induced decline in cardiac function. It remains unclear whether a direct interaction between LOX and MMPs exists; however, our experiments suggest a potential link between the two because LOX inhibition completely attenuated VO-induced increases in MMPs. Overall, our study demonstrated key cardioprotective effects of LOX inhibition against adverse cardiac remodeling due to chronic VO. NEW & NOTEWORTHY Although the primary role of lysyl oxidase (LOX) is to cross-link collagens, we found that elevated LOX during cardiac disease plays a key role in the progression of heart failure. Here, we show that inhibition of LOX in volume-overloaded rats prevented the development of cardiac dysfunction and improved ventricular collagen and matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles.